Morbidity
To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis. (NCT00000134)
Timeframe: Patients will be seen at baseline, monthly for six months, and then every three months until death or termination of the trial
| Intervention | participants (Number) |
|---|
| Intravenous Foscarnet | 88 |
| Intravenous Ganciclovir | 93 |
| Combination Therapy | 93 |
Mortality
(NCT00000136)
Timeframe: All patients enrolled will be followed until a common study closing date, which was chosen to provide a minimum of 1 year of follow-up for all patients enrolled in the trial.
| Intervention | participants (Number) |
|---|
| Foscarnet | 107 |
| Ganciclovir | 127 |
Survival
(NCT00000143)
Timeframe: 3 years
| Intervention | participants (Number) |
|---|
| Ganciclovir Implant and Oral Ganciclovir | 31 |
| Cidofovir IV (Intravenous) | 30 |
Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation.
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1.) a blood glycosylated hemoglobin (HbA1c) level < 6.5% (Normal:<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: <140mg/dL if <=50 years of age, <150 mg/dL for ages 50-60 years and <160 mg/dL for ages 60+) (NCT00014911)
Timeframe: One year status post participant receipt of final islet transplantation
| Intervention | Percent of Participants (Number) |
|---|
| Insulin Independence at One Year | Insulin Independence with One Transplant | Insulin Independence with Two Transplants | Insulin Independence with Three Transplants |
|---|
| Islet Transplantation | 44 | 14 | 17 | 14 |
Serum Creatinine Levels for Participants in the Extended Follow-up Study Phase
Seven participants from US sites were included in the extended follow-up. These participants were monitored yearly from year three post last transplantation (the original end of study follow-up) through August 30, 2010 (up to 9 years post first transplantation), at which point they were transferred to a new protocol (ITN040CT [NCT01309022]). Serum creatinine is a measure of renal function. Normal ranges are from 0.5 to 1.0 mg/dL for females and 0.7 to 1.2 mg/dL for males. (NCT00014911)
Timeframe: First transplantation through August 30, 2010 (up to 9 years)
| Intervention | mg/dL (Mean) |
|---|
| Islet Transplantation | 0.9 |
Percent of Participants With Partial Islet Function One Year Post Final Islet Transplantation.
Partial islet function definition: a fasting basal C-peptide level >= 0.3 ng/mL and a continuing need for insulin or suboptimal glycemic control (Note: C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making). Adequate glycemic control is defined by: 1) a blood HbA1c level <6.5%, 2) a blood glucose level after an overnight fast not exceeding 140 mg/dL more than three times in any week and, 3) a 2-hour postprandial blood glucose level not exceeding 180 mg/dL more than four times per week (NCT00014911)
Timeframe: One year post receipt of final islet transplantation
| Intervention | Percent of Participants (Number) |
|---|
| Islet Transplantation | 28 |
Percent of Participants With Detectable Fasting Basal C-Peptide Levels
C-peptide is a substance that the pancreas releases into the bloodstream in equal amounts to insulin, thereby showing how much insulin the body is making. C-peptide secretion is used to measure the function of transplanted islets. Higher levels indicate better islet function. Detectable fasting basal levels of C-peptide secretion are >=0.3 ng/ml. (NCT00014911)
Timeframe: Two years post first transplantation
| Intervention | Percent of Participants (Number) |
|---|
| Islet Transplantation | 70 |
Percent of Participants That Achieved Insulin Independence From First Transplant
Insulin independence: exogenous insulin not required and glycemic control is achieved as defined by maintaining 1) a blood glycosylated hemoglobin (HbA1c) level < 6.5% (Normal:<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher),2) a blood glucose level after an overnight fast not exceeding 140 mg per deciliter (dL) more than three times in any week (Normal: 70 to 120 mg/dL), and 3)not exceeding a 2-hour postprandial blood glucose level of 180 mg/dL more than four times per week (Normal: <140mg/dL if <=50 years of age, <150 mg/dL for ages 50-60 years and <160 mg/dL for ages 60+) (NCT00014911)
Timeframe: First transplantation until end of study (up to six years post final transplantation)
| Intervention | Percent of Participants (Number) |
|---|
| Islet Transplantation | 58 |
HbA1c Plasma Laboratory Values for Participants in the Extended Follow-up Study Phase
Seven participants from US sites were included in the extended follow-up. These participants were monitored yearly from year three post last transplantation (the original end of study follow-up) through August 30, 2010 (up to 9 years post first transplantation), at which point they were transferred to a new protocol (ITN040CT [NCT01309022]). Glycosylated hemoglobin (HbA1c) is a measure of the average plasma glucose concentration over prolonged periods of time. (Normal:<5.7%; pre-diabetes: 5.7% -6.4%; diabetes: 6.5% or higher) (NCT00014911)
Timeframe: First transplantation through August 30, 2010 (up to 9 years)
| Intervention | HbA1c Percentage (Mean) |
|---|
| Islet Transplantation | 6.2 |
The Difference in Linear Growth by Treatment Assignment at 1 Year Post Kidney Transplantation
Standardized Z-scores were computed following a formula using an age- and gender-specific calculation provided by the NHANES III 2000 Growth Data set. The Z-score system expresses anthropometric values of height as several standard deviations (SDs) below (e.g., a negative value) or above (a positive value) the reference mean or median value. In this study the measure was used to test whether there is a difference in the change in height between the treatment groups: Steroid-Based versus Steroid-Free (NCT00141037)
Timeframe: One year post kidney transplantation procedure
| Intervention | Standard Deviation Score (SDS) (Mean) |
|---|
| Steroid-Free Immunosuppression | 0.37 |
| Steroid-Based Immunosuppression | 0.35 |
Comparison by Treatment Assignment in the Number of Biopsy-Proven Acute Rejections Within 12 Months Post Kidney Transplantation
"Biopsy-proven acute renal (kidney) rejection [1, 2].~Diagnosis of acute rejection was made by renal biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection[2]~Ref: Racusen LC et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999" (NCT00141037)
Timeframe: Up to one year post kidney transplantation procedure
| Intervention | Rejection Events (Number) |
|---|
| Steroid-Free Immunosuppression | 18 |
| Steroid-Based Immunosuppression | 19 |
Percentage of Participants With Post-Transplant Diabetes Mellitus
(NCT00372229)
Timeframe: Up to 12 months
,
| Intervention | percentage of participants (Number) |
|---|
| Month 6 | Month 12 |
|---|
| Pre-emptive CMV Therapy | 1.3 | 0.7 |
| Valganciclovir CMV Prophylaxis | 2.7 | 3.4 |
Proteomics Parameter: CKD273
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273 was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
,
| Intervention | score on a scale (Mean) |
|---|
| Visit 6 (n=113, 114) | Visit 13 (n=102, 110) | Visit 15 (n=106, 102) |
|---|
| Pre-emptive CMV Therapy | 0.394 | 0.295 | 0.326 |
| Valganciclovir CMV Prophylaxis | 0.372 | 0.258 | 0.276 |
Creatinine Clearance at Month 12
Creatinine clearance was estimated using the Cockcroft-Gault formula. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | millilitre(s)/minute (Mean) |
|---|
| Valganciclovir CMV Prophylaxis | 61.1 |
| Pre-emptive CMV Therapy | 61.3 |
Number of Participants Who Died From Months 24 to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 8 | 9 | 10 | 12 | 16 | 17 |
| Valganciclovir CMV Prophylaxis | 3 | 6 | 8 | 11 | 14 | 14 |
Number of Participants Who Had Lost Their Transplant or Died up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 15 | 18 | 19 | 23 | 28 | 29 |
| Valganciclovir CMV Prophylaxis | 7 | 9 | 12 | 16 | 21 | 24 |
Number of Participants With Graft Rejections by CMV Status (Positive or Negative) of the Donor at Month 24 and Every 12 Months up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
| Intervention | Participants (Count of Participants) |
|---|
| 24 months: CMV Positive Donor72408743 | 24 months: CMV Positive Donor72408744 | 24 months: CMV Negative Donor72408743 | 24 months: CMV Negative Donor72408744 | 36 months: CMV Positive Donor72408743 | 36 months: CMV Positive Donor72408744 | 36 months: CMV Negative Donor72408743 | 36 months: CMV Negative Donor72408744 | 48 months: CMV Positive Donor72408743 | 48 months: CMV Positive Donor72408744 | 48 months: CMV Negative Donor72408743 | 48 months: CMV Negative Donor72408744 | 60 months: CMV Positive Donor72408743 | 60 months: CMV Positive Donor72408744 | 60 months: CMV Negative Donor72408743 | 60 months: CMV Negative Donor72408744 | 72 months: CMV Positive Donor72408743 | 72 months: CMV Positive Donor72408744 | 72 months: CMV Negative Donor72408743 | 72 months: CMV Negative Donor72408744 | 84 months: CMV Positive Donor72408743 | 84 months: CMV Positive Donor72408744 | 84 months: CMV Negative Donor72408743 | 84 months: CMV Negative Donor72408744 |
|---|
| No Rejections | At Least One Rejection |
|---|
| Valganciclovir CMV Prophylaxis | 26 |
| Valganciclovir CMV Prophylaxis | 65 |
| Pre-emptive CMV Therapy | 13 |
| Pre-emptive CMV Therapy | 59 |
| Pre-emptive CMV Therapy | 27 |
| Pre-emptive CMV Therapy | 52 |
| Pre-emptive CMV Therapy | 14 |
| Pre-emptive CMV Therapy | 58 |
| Valganciclovir CMV Prophylaxis | 27 |
| Valganciclovir CMV Prophylaxis | 64 |
| Valganciclovir CMV Prophylaxis | 28 |
| Pre-emptive CMV Therapy | 28 |
| Valganciclovir CMV Prophylaxis | 63 |
| Pre-emptive CMV Therapy | 51 |
| Valganciclovir CMV Prophylaxis | 15 |
| Pre-emptive CMV Therapy | 15 |
| Valganciclovir CMV Prophylaxis | 42 |
| Pre-emptive CMV Therapy | 57 |
Proteomics Parameter: CMV
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CMV was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
,
| Intervention | score on a scale (Mean) |
|---|
| Visit 6 (n=113, 114) | Visit 13 (n=102, 110) | Visit 15 (n=106, 102) |
|---|
| Pre-emptive CMV Therapy | -0.018 | -0.05 | -0.068 |
| Valganciclovir CMV Prophylaxis | -0.004 | 0.036 | -0.073 |
Relationship Between Proteomics Pattern and Participant Survival
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273, CMV, and nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
,
| Intervention | score on a scale (Mean) |
|---|
| CKD273:Visit 6: Did not Survive (n=2, 1) | CKD273:Visit 6: Survived (n=111, 113) | CKD273:Visit 13: Did not Survive (n=1, 1) | CKD273:Visit 13: Survived (n=101, 109) | CKD273:Visit 15: Survived (n=106, 102) | CMV:Visit 6: Did not Survive (n=2, 1) | CMV:Visit 6: Survived (n=111, 113) | CMV:Visit 13: Did not Survive (n=1, 1) | CMV:Visit 13: Survived (n=101, 109) | CMV:Visit 15: Survived (n=106, 102) | Nephropathy:Visit 6: Did not Survive (n=2, 1) | Nephropathy:Visit 6: Survived (n=111, 113) | Nephropathy:Visit 13: Did not Survive (n=1, 1) | Nephropathy:Visit 13: Survived (n=101, 109) | Nephropathy:Visit 15: Survived (n=106, 102) |
|---|
| Pre-emptive CMV Therapy | 0.500 | 0.393 | 0.500 | 0.293 | 0.326 | -0.900 | -0.010 | -0.300 | -0.048 | -0.068 | -0.100 | 0.124 | -0.800 | 0.008 | 0.102 |
| Valganciclovir CMV Prophylaxis | 0.400 | 0.371 | 0.700 | 0.253 | 0.276 | 1.150 | -0.025 | 0.400 | 0.033 | -0.073 | 0.150 | 0.101 | 1.800 | -0.068 | 0.019 |
Relationship Between Proteomics Pattern and Graft Survival
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273, CMV, and nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | score on a scale (Mean) |
|---|
| CKD273:Visit 6: With Graft Loss (n=1, 4) | CKD273:Visit 6: Without Graft Loss (n=112, 110) | CKD273:Visit 13: Without Graft Loss (n=102, 109) | CKD273:Visit 15: With Graft Loss (n=2, 0) | CKD273:Visit 15: Without Graft Loss (n=104, 102) | CMV:Visit 6: With Graft Loss (n=1, 4) | CMV:Visit 6: Without Graft Loss (n=112, 110) | CMV:Visit 13: Without Graft Loss (n=102, 109) | CMV:Visit 15: With Graft Loss (n=2, 0) | CMV:Visit 15: Without Graft Loss (n=104, 102) | Nephropathy:Visit 6: With Graft Loss (n=1, 4) | Nephropathy:Visit 6:Without Graft Loss (n=112,110) | Nephropathy:Visit 13:Without Graft Loss(n=102,109) | Nephropathy:Visit 15: With Graft Loss (n=2, 0) | Nephropathy:Visit15: Without Graft Loss(n=104,102) |
|---|
| Valganciclovir CMV Prophylaxis | 0.400 | 0.371 | 0.258 | 0.600 | 0.270 | -0.500 | 0.000 | 0.036 | 0.100 | -0.076 | -0.500 | 0.107 | -0.050 | 1.350 | -0.007 |
Relationship Between Proteomics Pattern and Graft Survival
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of CKD273, CMV, and nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | score on a scale (Mean) |
|---|
| CKD273:Visit 6: With Graft Loss (n=1, 4) | CKD273:Visit 6: Without Graft Loss (n=112, 110) | CKD273:Visit 13: With Graft Loss (n=0, 1) | CKD273:Visit 13: Without Graft Loss (n=102, 109) | CKD273:Visit 15: Without Graft Loss (n=104, 102) | CMV:Visit 6: With Graft Loss (n=1, 4) | CMV:Visit 6: Without Graft Loss (n=112, 110) | CMV:Visit 13: With Graft Loss (n=0, 1) | CMV:Visit 13: Without Graft Loss (n=102, 109) | CMV:Visit 15: Without Graft Loss (n=104, 102) | Nephropathy:Visit 6: With Graft Loss (n=1, 4) | Nephropathy:Visit 6:Without Graft Loss (n=112,110) | Nephropathy:Visit 13: With Graft Loss (n=0, 1) | Nephropathy:Visit 13:Without Graft Loss(n=102,109) | Nephropathy:Visit15: Without Graft Loss(n=104,102) |
|---|
| Pre-emptive CMV Therapy | 0.800 | 0.379 | 0.500 | 0.293 | 0.326 | -0.300 | -0.007 | -0.300 | -0.048 | -0.068 | 1.100 | 0.086 | -0.800 | 0.008 | 0.102 |
Number of Participants Who Had Lost Their Transplant up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 8 | 10 | 10 | 12 | 13 | 13 |
| Valganciclovir CMV Prophylaxis | 4 | 4 | 5 | 6 | 8 | 11 |
Number of Participants With Active CMV Infection After Month 24 and Every 12 Months up to Month 84
Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 59 | 59 | 59 | 59 | 60 | 60 |
| Valganciclovir CMV Prophylaxis | 16 | 16 | 16 | 16 | 17 | 17 |
Number of Participants With Active CMV Infection Who Had Lost Their Transplant up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 5 | 7 | 7 | 9 | 9 | 9 |
| Valganciclovir CMV Prophylaxis | 0 | 0 | 0 | 0 | 0 | 1 |
Number of Participants With CMV Disease After Month 24 and Every 12 Months up to Month 84
CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 23 | 23 | 23 | 24 | 24 | 24 |
| Valganciclovir CMV Prophylaxis | 7 | 7 | 7 | 7 | 7 | 7 |
Number of Participants With CMV Disease From Baseline to Month 24 and Every 12 Months up to Month 84
CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 23 | 23 | 23 | 24 | 24 | 24 |
| Valganciclovir CMV Prophylaxis | 7 | 7 | 7 | 7 | 7 | 7 |
Proteomics Parameter: Nephropathy
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. The proteomics of nephropathy was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
,
| Intervention | score on a scale (Mean) |
|---|
| Visit 6 (n=113, 114) | Visit 13 (n=102, 110) | Visit 15 (n=106, 102) |
|---|
| Pre-emptive CMV Therapy | 0.122 | 0.001 | 0.102 |
| Valganciclovir CMV Prophylaxis | 0.102 | -0.05 | 0.019 |
Number of Participants With CMV Syndrome From Baseline to Month 24 and Every 12 Months up to Month 84
CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 20 | 20 | 20 | 21 | 21 | 21 |
| Valganciclovir CMV Prophylaxis | 7 | 7 | 7 | 7 | 7 | 7 |
Number of Participants With CMV Tissue Invasive Disease From Baseline to Month 24 and Every 12 Months up to Month 84
CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 5 | 5 | 5 | 5 | 5 | 5 |
| Valganciclovir CMV Prophylaxis | 4 | 4 | 4 | 4 | 4 | 4 |
Number of Participants With CMV Viremia (Active CMV Infection) From Baseline to Month 24 and Every 12 Months up to Month 84
Viremia (active CMV Infection) was defined as PCR ≥ 400 copies/ml. (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 59 | 59 | 59 | 59 | 60 | 60 |
| Valganciclovir CMV Prophylaxis | 16 | 16 | 16 | 16 | 17 | 17 |
Number of Participants Without Active CMV Infection Who Had Lost Their Transplant up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | Participants (Count of Participants) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 3 | 3 | 3 | 3 | 4 | 4 |
| Valganciclovir CMV Prophylaxis | 4 | 4 | 5 | 6 | 8 | 10 |
Percentage of Participants Surviving at Month 24 and Every 12 Months up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | percentage of participants (Number) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 94.70 | 94.04 | 93.38 | 92.05 | 89.40 | 88.74 |
| Valganciclovir CMV Prophylaxis | 97.97 | 95.95 | 94.59 | 92.57 | 90.54 | 90.54 |
Percentage of Participants With Graft Survival at Month 24 and Every 12 Months up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | percentage of participants (Number) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 94.70 | 93.38 | 93.38 | 92.05 | 91.39 | 91.39 |
| Valganciclovir CMV Prophylaxis | 97.30 | 97.30 | 96.62 | 95.95 | 94.59 | 92.57 |
Percentage of Participants With Graft Survival or Participant Survival at Month 24 and Every 12 Months up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | percentage of participants (Number) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 90.07 | 88.08 | 87.42 | 84.77 | 81.46 | 80.79 |
| Valganciclovir CMV Prophylaxis | 95.27 | 93.92 | 91.89 | 89.19 | 85.81 | 83.78 |
Percentage of Participants With at Least One Treated and Biopsy-Proven Acute Rejection Episode Within 12 Months
(NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 18.2 |
| Pre-emptive CMV Therapy | 13.2 |
Days of Hospitalization
(NCT00372229)
Timeframe: Up to 12 months
| Intervention | days (Median) |
|---|
| Valganciclovir CMV Prophylaxis | 26.5 |
| Pre-emptive CMV Therapy | 32 |
Kaplan-Meier Estimate of the Percentage of Participants (With Versus Without Active CMV Infection) on Pre-emptive CMV Therapy With First Occurrence of Graft Loss at Month 84
An analysis for the time to first occurrence of graft loss within month 84 (by means of Kaplan-Meier analysis) was done for all patients who suffered at least once from acute CMV infection (CMV viremia) during this study versus all patients who did not suffer from acute CMV infection (CMV viremia) during the study. Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). (NCT00372229)
Timeframe: Up to 84 months
| Intervention | percentage of participants (Number) |
|---|
| Pre-emptive CMV Therapy, With CMV Infection at Month 84 | 17.9 |
| Pre-emptive CMV Therapy, No CMV Infection at Month 84 | 5.8 |
Kaplan-Meier Estimate of the Percentage of Participants (With Versus Without Active CMV Infection) on Valganciclovir CMV Prophylaxis With First Occurrence of Graft Loss at Month 84
An analysis for the time to first occurrence of graft loss within month 84 (by means of Kaplan-Meier analysis) was done for all patients who suffered at least once from acute CMV infection (CMV viremia) during this study versus all patients who did not suffer from acute CMV infection (CMV viremia) during the study. Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). (NCT00372229)
Timeframe: Up to 84 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis,With CMV Infection at Month 84 | 8.3 |
| Valganciclovir CMV Prophylaxis, No CMV Infection at Month 84 | 11.5 |
Percentage of Participants Surviving at Month 12
(NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 98 |
| Pre-emptive CMV Therapy | 98.7 |
Percentage of Participants With Active CMV Infections Not Responding to Valganciclovir or IV Ganciclovir Treatment
Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 11.8 |
| Pre-emptive CMV Therapy | 18.3 |
Percentage of Participants With Active Cytomegalovirus (CMV) Infection Within 12 Months
Active CMV infection was defined as plasma polymerase chain reaction (PCR) ≥ 400 copies/millilitre (ml). (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 14.1 |
| Pre-emptive CMV Therapy | 42.6 |
Percentage of Participants With Any Opportunistic Infection Within 12 Months
(NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 31.1 |
| Pre-emptive CMV Therapy | 37.7 |
Percentage of Participants With CMV Disease Within 12 Months Including CMV Syndrome and Tissue Invasive Disease
CMV disease comprises the two components of CMV syndrome as well as CMV tissue invasive disease. CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). CMV tissue invasive disease was defined as viremia according plasma PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 5.6 |
| Pre-emptive CMV Therapy | 16.9 |
Percentage of Participants With CMV Syndrome Within 12 Months
CMV syndrome was defined as viremia according to plasma PCR ≥ 400 copies/ml and at least one of the following signs: fever of ≥38 °C; new or increased malaise (malaise defined as normal activity reduced >50%; cannot work or unable to care for self; leukopenia on 2 successive measurements separated by at least 24 hours thrombocytopenia; elevation of hepatic transaminases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to at least 2 x upper limit of normal (ULN). (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 5.6 |
| Pre-emptive CMV Therapy | 14.6 |
Percentage of Participants With CMV Tissue Invasive Disease Within 12 Months
CMV tissue invasive disease was defined as viremia: PCR ≥ 400 copies/ml and clinical evidence of localized CMV infection (CMV inclusion cells or in situ detection of CMV antigen or deoxyribonucleic acid [DNA] by immunostaining or hybridization, respectively), cerebral spinal fluid [CSF]) and/or relevant symptoms or signs of organ dysfunction. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 3.3 |
| Pre-emptive CMV Therapy | 3.6 |
Percentage of Participants With Graft Loss at Month 84
(NCT00372229)
Timeframe: Up to 84 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 7.43 |
| Pre-emptive CMV Therapy | 8.61 |
Percentage of Participants With Graft Survival at Month 12
(NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 98.6 |
| Pre-emptive CMV Therapy | 96.0 |
Percentage of Participants With Leukopenia Within 12 Months
Leukopenia: white blood cell (WBC) of < 3,500/microlitre (μL) and < 1,000/μL (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 35.1 |
| Pre-emptive CMV Therapy | 26.5 |
Percentage of Participants With Neutropenia Within 12 Months
Neutropenia: absolute neutrophil count (ANC) < 750/μL within 12 months. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | percentage of participants (Number) |
|---|
| Valganciclovir CMV Prophylaxis | 16.9 |
| Pre-emptive CMV Therapy | 12.6 |
Time to Occurrence of First Viremia Within 12 Months
Viremia was defined as plasma PCR ≥ 400 copies/ml. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | days (Median) |
|---|
| Valganciclovir CMV Prophylaxis | NA |
| Pre-emptive CMV Therapy | NA |
Urine Proteomic Pattern at Month 12
Proteomics is the complete set of proteins expressed by an organism, tissue, or cell. Urine proteomic pattern was measured on a scale between -1, indicating no graft alteration, and +1, indicating graft alteration. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Valganciclovir CMV Prophylaxis | -0.1057 |
| Pre-emptive CMV Therapy | 0.1452 |
Viral Burden at Viremia
Time-weighted area under the curve (AUC) of the polymerase chain reaction (PCR). Viremia was defined as plasma PCR ≥ 400 copies/ml. (NCT00372229)
Timeframe: Up to 12 months
| Intervention | copies/ml*days (Mean) |
|---|
| Valganciclovir CMV Prophylaxis | 5309.83 |
| Pre-emptive CMV Therapy | 3765.8 |
Creatinine Clearance at Month 24 and Every 12 Months up to Month 84
Creatinine Clearance estimated by Cockcroft-Gault formula. (NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | millimiters/minute (Mean) |
|---|
| 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Pre-emptive CMV Therapy | 62.9 | 64.5 | 62.6 | 64.9 | 64.7 | 60.8 |
| Valganciclovir CMV Prophylaxis | 63.2 | 63.9 | 63.1 | 62.2 | 63.3 | 59.5 |
Number of Graft Rejections by CMV Status (Positive or Negative) of the Donor at Month 24 and Every 12 Months up to Month 84
(NCT00372229)
Timeframe: From Month 24 to Month 84
,
| Intervention | graft rejections (Number) |
|---|
| 24 months: CMV Positive Donor | 24 months: CMV Negative Donor | 36 months: CMV Positive Donor | 36 months: CMV Negative Donor | 48 months: CMV Positive Donor | 48 months: CMV Negative Donor | 60 months: CMV Positive Donor | 60 months: CMV Negative Donor | 72 months: CMV Positive Donor | 72 months: CMV Negative Donor | 84 months: CMV Positive Donor | 84 months: CMV Negative Donor |
|---|
| Pre-emptive CMV Therapy | 48 | 27 | 51 | 28 | 51 | 28 | 52 | 29 | 53 | 29 | 53 | 31 |
| Valganciclovir CMV Prophylaxis | 39 | 20 | 42 | 20 | 45 | 21 | 46 | 21 | 48 | 21 | 48 | 21 |
Number of Participants Who Died Within 6 Months Post-Transplantation
(NCT00497796)
Timeframe: 6 months post-transplant
| Intervention | participants (Number) |
|---|
| Maribavir 100 mg BID | 9 |
| Ganciclovir 1000 mg TID | 6 |
Number of Participants With EC-confirmed CMV Disease Within 100 Days Post-Transplantation
All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction [PCR] assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002. (NCT00497796)
Timeframe: 100 days post-transplant
| Intervention | participants (Number) |
|---|
| Maribavir 100 mg BID | 10 |
| Ganciclovir 1000 mg TID | 0 |
Number of Participants With Endpoint Committee (EC)-Confirmed Cytomegalovirus (CMV) Disease Within 6 Months Post-Transplantation
All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease), were adjudicated by an independent, blinded EC. Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction [PCR] assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002. (NCT00497796)
Timeframe: 6 months post-transplant
| Intervention | number of participants with event (Number) |
|---|
| Maribavir 100 mg BID | 14 |
| Ganciclovir 1000 mg TID | 10 |
Time to Onset of CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
All investigator-determined (protocol-defined) cases of CMV disease (i.e., symptomatic CMV infection or CMV organ disease) were adjudicated by an independent, blinded EC. CMV infection was assessed by pp65 Antigenemia or CMV DNA PCR from a central or local lab. CMV organ disease was defined as described by Ljungman et al., 2002. (NCT00497796)
Timeframe: 6 months post-transplant
| Intervention | days (Median) |
|---|
| Maribavir 100 mg BID | 45 |
| Ganciclovir 1000 mg TID | 127 |
Number of Participants With Acute Graft Rejection
Rejection was assessed by examining a liver biopsy sample. Diagnosis of graft rejection included a global assessment grade and a rejection activity index score. (NCT00497796)
Timeframe: 26 weeks post-transplant
,
| Intervention | participants (Number) |
|---|
| 100 days post-transplant | 6 months post-transplant |
|---|
| Ganciclovir 1000 mg TID | 19 | 23 |
| Maribavir 100 mg BID | 16 | 20 |
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 6 Months Post-Transplantation
Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy. (NCT00497796)
Timeframe: 6 months post-transplant
,
| Intervention | participants (Number) |
|---|
| pp65 antigenemia assay | CMV DNA PCR assay | pp65 antigenemia or CMV DNA PCR assay | Initiation of anti-CMV therapy |
|---|
| Ganciclovir 1000 mg TID | 49 | 52 | 64 | 39 |
| Maribavir 100 mg BID | 63 | 72 | 81 | 46 |
Number of Participants With Investigator-determined CMV Disease
Symptomatic CMV infection was defined as: CMV infection detected by a positive result from a CMV laboratory assay from at least one central laboratory assay (pp65 antigenemia or CMV DNA polymerase chain reaction [PCR] assay in plasma) and fever >/=38 °C on >/=2 occasions >/=24 hours apart within a 7-day period and at least one of the following: new or increased malaise, two successive measurements of leucopenia (white blood cell [WBC] count <3500/mm3 or a WBC count decrease of 20% if the cell count prior to onset of clinical symptoms was >4000/mm3) >/=24 hours apart, atypical lymphocytosis >/=5%, and thrombocytopenia. CMV organ disease was defined as described by Ljungman et al., 2002. (NCT00497796)
Timeframe: Through 6 months post-transplant (Day 1 to 100 days and 6 months post-transplant)
,
| Intervention | participants (Number) |
|---|
| 100 days post-transplant | 6 months post-transplant |
|---|
| Ganciclovir 1000 mg TID | 3 | 18 |
| Maribavir 100 mg BID | 17 | 22 |
Number of Participants With Retransplantation
(NCT00497796)
Timeframe: Through 6 months post-transplant (From Day 1 to 100 days and 6 months post-transplant)
,
| Intervention | participants (Number) |
|---|
| At 100 days post-transplant | At 6 months post-transplant |
|---|
| Ganciclovir 1000 mg TID | 2 | 2 |
| Maribavir 100 mg BID | 1 | 2 |
Percent of Participants With Signs of Bone Marrow Suppression
Bone marrow suppression was assessed by the occurrence of adverse events (AEs) of investigator-reported leukopenia, neutropenia, thrombocytopenia, and pancytopenia; absolute neutrophil count (ANC) <1000/mm3; white blood cell (WBC) count toxicity grade shifts from 0-2 at baseline to a maximum of 3-4 post-baseline; and use of hematopoietic growth factors during the 6 month post-transplant period. (NCT00497796)
Timeframe: 15 weeks
,
| Intervention | percent of participants (Number) |
|---|
| Hematology AEs | ANC <1000/mm3 | WBC count toxicity grade shifts | Use of hematopoietic growth factors |
|---|
| Ganciclovir 1000 mg TID | 21 | 16 | 21 | 20 |
| Maribavir 100 mg BID | 14 | 9 | 16 | 15 |
Plasma Concentration of Maribavir During Treatment
For the first 16 subjects to have PK profiling performed, PK sampling was collected at Weeks 2, 6 and 10. For subsequent subjects that have PK profiling performed, PK sampling was collected at Weeks 2 and 6. Samples were collected 12 hours after the morning dose of maribavir. Permissible assessment windows for pharmacokinetic profile sampling purposes were +/- 5 days for each sampling day. Samples for determination of maribavir concentration were analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. For plasma, the minimum detectable concentration for maribavir was 0.2 μg/mL. (NCT00497796)
Timeframe: 12 hours post-dose after 2, 6, and 10 weeks of treatment
| Intervention | μg/mL (Mean) |
|---|
| 2 weeks, n=10 | 6 weeks, n=7 | 10 weeks, n=8 |
|---|
| Maribavir 100 mg BID | 1.65 | 1.36 | 1.55 |
Number of Participants With CMV Infection or EC-confirmed CMV Disease Within 100 Days Post-Transplantation
Incidence of CMV infection or EC-confirmed CMV disease within the 6-month post-transplant period included in this section were defined (1) with infection assessed by pp65 antigenemia assay; (2) with infection assessed by CMV DNA PCR; (3) with infection assessed by either assay (pp65 antigenemia or CMV DNA PCR); and (4) with infection assessed by initiation of anti-CMV therapy. (NCT00497796)
Timeframe: 100 days post-transplant
,
| Intervention | participants (Number) |
|---|
| pp65 antigenemia assay | CMV DNA PCR assay | pp65 antigenemia or CMV DNA PCR assay | Initiation of anti-CMV therapy |
|---|
| Ganciclovir 1000 mg TID | 19 | 18 | 24 | 5 |
| Maribavir 100 mg BID | 49 | 59 | 68 | 37 |
Number of Participants With Adverse Events
This will be measured by the number of the CMV+ participants with adverse events occurring when receiving oral GCV. (NCT00530218)
Timeframe: From first ganciclovir positive test, after day 21 post-hematopoietic cell transplant
| Intervention | Participants (Count of Participants) |
|---|
| Haptoglobin | Hemoglobin | Hemolysis | Leukocytes | Lymphopenia | Neutrophils/granulocytes | Platelets | pRBCs | aGVHD | cGVHD | Palpitations | Supraventricular and nodal arrhythmia | Cardiac General - Other | Hypertension | Hypotension | Edema | INR | Fatigue | Fever | Insomnia | Rigors/Chills | Sweating | Weight loss | Bruising | Skin - Other | Dry Skin | Flushing | Hair Loss / Alopecia | Pigmentation Changes | Pruritus/Itching | Rash/Desquamation | Rash/Desquamation w GVHD | Wound Complication, Non-infection | Cushingoid Appearance | Endocrine - Other | Thyroid Function, Low (Hypothyroidism) | Anorexia | Constipation | Dehydration | Diarrhea | Diarrhea with GVHD | Dry mouth/Salivary Gland (Xerostomia) | Esophagitis | Flatulence | Gastritis | Gastrointestinal - Other | Heartburn/Dyspepsia | Mucositis/Stomatitis | Nausea | Stomatitis/pharyngitis (Oral/Pharyngeal Mucositis) | Taste Alteration (Dysgeusia) | Vomiting | Hematuria (in the absence of vaginal bleeding) | Hemorrhage/bleeding w/ grade 3 or 4 thrombocytopni | Hemorrhage/bleeding w/o grade 3 or 4 thrombocytope | Hemorrhage, pulmonary/upper respiratory | Hemorrhage/Bleeding - Other | Petechiae/purpura | Bilirubin with GVHD | Febrile Neutropenia | Infection - Other | Infection w/ unknown ANC | Infection - Bacterial | Infection - Fungal | Infection - Viral | Lymphatics | ALT, SGPT | AST, SGOT | Albumin, serum-low (hypoalbuminemia) | Alkaline phosphatase | Bilirubin (hyperbilirubinemia) | CPK (creatine phosphokinase) | Calcium, serum-high (hypercalcemia) | Calcium, serum-low (hypocalcemia) | Cholesterol, serum-high (hypercholesteremia) | Creatinine | Glucose, serum-high (hyperglycemia) | Magnesium, serum-high (hypermagnesemia) | Magnesium, serum-low (hypomagnesemia) | Metabolic/Laboratory - Other | Phosphate, serum-low (hypophosphatemia) | Potassium, serum-high (hyperkalemia) | Potassium, serum-low (hypokalemia) | Proteinuria | Sodium, serum-low (hyponatremia) | Uric acid, serum-high (hyperuricemia) | Muscle weakness, generalized or specific area | Musculoskeletal/Soft Tissue - Other | Myositis (inflammation/damage of muscle) | Confusion | Dizziness | Memory Impairment | Mood Alteration | Neurology - Other | Neuropathy: Motor | Neuropathy: Sensory | Speech Impairment | Syncope | Tremor | Dry eye syndrome | Ocular/Visual - Other | Ophthalmoplegia/diplopia (double vision) | Pain | Adult Respiratory Distress Syndrome (ARDS) | Cough | Dyspnea (shortness of breath) | Hypoxia | Pleural effusion (non-malignant) | Pneumonitis/pulmonary infiltrates | Pulmonary/Upper Respiratory - Other | Urinary frequency/urgency | Urinary retention (including neurogenic bladder) | Thrombosis/thrombus/embolism |
|---|
| CMV Reactivation Patients With GCV | 1 | 31 | 1 | 22 | 2 | 12 | 26 | 17 | 21 | 1 | 1 | 19 | 1 | 13 | 5 | 8 | 1 | 21 | 10 | 3 | 6 | 1 | 3 | 2 | 3 | 5 | 4 | 4 | 5 | 3 | 3 | 19 | 1 | 15 | 2 | 1 | 15 | 1 | 16 | 4 | 4 | 2 | 2 | 4 | 2 | 6 | 4 | 1 | 22 | 16 | 5 | 14 | 4 | 2 | 2 | 1 | 1 | 1 | 5 | 1 | 1 | 3 | 13 | 3 | 8 | 1 | 31 | 23 | 25 | 11 | 8 | 1 | 1 | 20 | 23 | 20 | 24 | 4 | 27 | 1 | 21 | 7 | 16 | 1 | 15 | 5 | 3 | 2 | 1 | 1 | 5 | 1 | 11 | 4 | 1 | 3 | 1 | 1 | 12 | 2 | 4 | 1 | 25 | 2 | 7 | 7 | 2 | 1 | 6 | 2 | 1 | 1 | 1 |
Compliance Rate Among Patients With CMV Reactivation
CMV reactivation patients completed 6-week GCV therapy. (NCT00530218)
Timeframe: From first ganciclovir positive test to the end of the 6th week GCV therapy
| Intervention | participants (Number) |
|---|
| Compliance | No Compliance |
|---|
| Compliance Among Patients With CMV Reactivation | 26 | 8 |
Overall Mortality
Overall mortality amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
,
| Intervention | events (Number) |
|---|
| number of deaths | number of alive |
|---|
| IV Ganciclovir | 16 | 66 |
| Placebo | 11 | 53 |
Platelet Transfusions
Platelet transfusions per patient (NCT01335932)
Timeframe: by 35 days post-randomization
| Intervention | transfusions (Median) |
|---|
| IV Ganciclovir | 1 |
| Placebo | 1 |
Number of Mechanical Ventilated Days
Number of mechanical ventilated days amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 7.05 |
| Placebo | 9.05 |
AUC Plasma Levels of IL-10
AUC Plasma levels of IL-10 from day 0 to day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | 0.36 |
| Placebo | 0.35 |
AUC Plasma Levels of IL-6
AUC Plasma levels of IL-6 from day 0 to day 28 (NCT01335932)
Timeframe: Day 0 to 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | 0.68 |
| Placebo | 0.75 |
AUC Plasma Levels of IL-8
AUC Plasma levels of IL-8 from day 0 to day 28 (NCT01335932)
Timeframe: Day 0 to 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | 1.15 |
| Placebo | 1.13 |
AUC Plasma Levels of Soluble ICAM-1
AUC Plasma levels of soluble ICAM-1 from day 0 to day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | 4.78 |
| Placebo | 4.65 |
AUC Plasma Levels of TNF-a
AUC Plasma levels of TNF-a from day 0 to day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | -0.14 |
| Placebo | -0.14 |
BAL Levels of IL-6
Levels of IL-6 from BALs at 7 days post-randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 1.01 |
| Placebo | 1.66 |
BAL Levels of IL-8
Levels of IL-8 in BALs at day 7 (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 2.21 |
| Placebo | 2.61 |
BAL Levels of TNFa
Levels of TNFa in BALs at day 7 (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 0.18 |
| Placebo | 0.46 |
CMV AUC in Blood
CMV AUC in blood from day 0 to day 28 (NCT01335932)
Timeframe: Day 0 to 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | 0.11 |
| Placebo | 0.39 |
CMV AUC in Throat
CMV AUC in Throat from day 0 to day 28 (NCT01335932)
Timeframe: Day 0 to 28 days post-randomization
| Intervention | IU*day/mL (Mean) |
|---|
| IV Ganciclovir | 0.03 |
| Placebo | 0.17 |
CMV Peak Viral Load in Blood
CMV Peak Viremia in blood at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 IU/mL (Mean) |
|---|
| IV Ganciclovir | 0.24 |
| Placebo | 0.89 |
Duration of Mechanical Ventilation as Assessed by Ventilator Days
Number of days of mechanical ventilation duration as assessed by ventilator days (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 6.95 |
| Placebo | 8.5 |
Duration of Mechanical Ventilation as Assessed by Ventilator Free Days
Number of days of mechanical ventilation duration as assessed by ventilator free days (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 18.71 |
| Placebo | 15.97 |
Length of Stay
Hospital days alive and not hospitalized by day 180 (NCT01335932)
Timeframe: by 180 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 145.13 |
| Placebo | 145.94 |
Length of Stay
Hospital days alive and not hospitalized by day 28 (NCT01335932)
Timeframe: by 28 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 9.96 |
| Placebo | 8.72 |
Number of Days Alive and Not in the ICU
Number of ICU days alive and not in the ICU by day 28 (NCT01335932)
Timeframe: by 28 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 10.02 |
| Placebo | 10.97 |
Number of Days in ICU Amongst Subjects by Day 28
Number of days in ICU amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: 28 days
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 16.73 |
| Placebo | 17.79 |
Number of Days in the Hospital
Number of days in the hospital amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 6.21 |
| Placebo | 5.53 |
Number of Days in the ICU
Number of days in the ICU amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 10.20 |
| Placebo | 11.83 |
Number of Hospital-free Days
Number of hospital-free days amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 10.22 |
| Placebo | 9.87 |
Number of Hospital-free Days Among Subjects by Day 28
Number of hospital-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: 28 days
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 3.54 |
| Placebo | 4.59 |
Number of ICU-free Days
Number of ICU-free days amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 15.38 |
| Placebo | 13.89 |
Number of ICU-free Days Amongst Subjects by Day 28
Number of ICU-free days amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: 28 days
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 7.73 |
| Placebo | 8.15 |
Number of Mechanically Ventilated Days Among Subjects by Day 28
Number of mechanically ventilated days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: 28 days
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 13.4 |
| Placebo | 14.42 |
Number of Ventilator-free Days
Number of ventilator-free days amongst subjects who survive at least 7 days after randomization (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 19.17 |
| Placebo | 17.97 |
Number of Ventilator-free Days Among Subjects by Day 28
Number of ventilator-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: 28 days
| Intervention | days (Mean) |
|---|
| IV Ganciclovir | 11.4 |
| Placebo | 12.45 |
Peak Plasma Levels of IL-10
Peak Plasma levels of IL-10 at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 0.88 |
| Placebo | 0.82 |
Peak Plasma Levels of IL-6
Peak Plasma levels of IL-6 at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 1.57 |
| Placebo | 1.56 |
Peak Plasma Levels of IL-8
Peak Plasma levels of IL-8 at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 1.67 |
| Placebo | 1.66 |
Peak Plasma Levels of Soluble ICAM-1
Peak Plasma levels of soluble ICAM-1 from day 0 to day 28 (NCT01335932)
Timeframe: Day 0 to 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 5.52 |
| Placebo | 5.57 |
Peak Plasma Levels of TNF-a
Peak Plasma levels of TNF-a at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 0.16 |
| Placebo | 0.17 |
Plasma Levels of IL-6
Plasma levels of IL-6 at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 0.35 |
| Placebo | 0.59 |
Plasma Levels of IL-6
Plasma levels of IL-6. (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 0.87 |
| Placebo | 0.92 |
Plasma Levels of IL-8
Levels of IL-8 in plasma at day 7 (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 1.38 |
| Placebo | 1.38 |
Plasma Levels of IL-8
Plasma levels of IL-8 at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 1.09 |
| Placebo | 1.27 |
Plasma Levels of Soluble ICAM-1
Plasma levels of soluble ICAM-1 at day 28 (NCT01335932)
Timeframe: at 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 5.34 |
| Placebo | 5.48 |
Plasma Levels of Soluble ICAM-1
Plasma levels of soluble ICAM-1 at day 7 (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | 5.43 |
| Placebo | 5.45 |
Plasma Levels of TNF a
Plasma levels of TNF a at day 7.Cytokines are summarized on log 10 scale. When logged value is negative, the raw value would be less than 1. (NCT01335932)
Timeframe: at 7 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | -0.07 |
| Placebo | -0.1 |
Plasma Levels of TNF a
Plasma levels of TNF a from day 0 to day 28 (NCT01335932)
Timeframe: Day 0 to 28 days post-randomization
| Intervention | log 10 pg/mL (Mean) |
|---|
| IV Ganciclovir | -0.06 |
| Placebo | -0.11 |
Red Blood Cell Transfusions Required Per Patients
Red blood cell transfusions required per patients by day 35 (NCT01335932)
Timeframe: by 35 days post-randomization
| Intervention | transfusions (Median) |
|---|
| IV Ganciclovir | 2 |
| Placebo | 1 |
Serum IL-6 Level
Change between baseline and 14 days post-randomization between placebo & ganciclovir groups (NCT01335932)
Timeframe: Baseline and Day 14
| Intervention | pg/mL (Mean) |
|---|
| IV Ganciclovir | -0.79 |
| Placebo | -0.79 |
SF-36 Functional Assessment Mental Component
Mental Component Summary at 180 days post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (NCT01335932)
Timeframe: at 180 days post-randomization
| Intervention | scores on a scale (Mean) |
|---|
| IV Ganciclovir | 45.55 |
| Placebo | 44.08 |
SF-36 Functional Assessment Mental Component on Day 1
SF-36 Mental Component Summary at 1 day post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (NCT01335932)
Timeframe: at 1 day post-randomization
| Intervention | scores on a scale (Mean) |
|---|
| IV Ganciclovir | 43.83 |
| Placebo | 42.73 |
SF-36 Functional Assessment Physical Component
Physical Component Summary at 180 days post- randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability (NCT01335932)
Timeframe: at 180 days post-randomization
| Intervention | scores on a scale (Mean) |
|---|
| IV Ganciclovir | 35.51 |
| Placebo | 38.17 |
SF-36 Health Survey
Physical Component Summary of SF-36. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability. (NCT01335932)
Timeframe: at 1 day post-randomization
| Intervention | scores on a scale (Mean) |
|---|
| IV Ganciclovir | 36.37 |
| Placebo | 35 |
Time to Neutropenia
Time to neutropenia by 35 days post-randomization (NCT01335932)
Timeframe: by 35 days post-randomization
| Intervention | days (Number) |
|---|
| IV Ganciclovir | 0 |
| Placebo | 0 |
Bacteremia and Fungemia Outcomes
Bacteremia and fungemia outcomes among subjects who survive at least 7 days (NCT01335932)
Timeframe: at 7 days post-randomization
,
| Intervention | events (Number) |
|---|
| number of events | number of no events |
|---|
| IV Ganciclovir | 15 | 67 |
| Placebo | 9 | 55 |
Bacteremia and Fungemia Outcomes in Mechanically Ventilated Subjets
Bacteremia and fungemia events among subjects who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: at 7 through 14 days post-randomization
,
| Intervention | events (Number) |
|---|
| number of events | number of no events |
|---|
| IV Ganciclovir | 6 | 24 |
| Placebo | 9 | 24 |
Mortality Among Subjects Mechanically Ventilated From Day 7 to 14
Mortality among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization (NCT01335932)
Timeframe: 28 days
,
| Intervention | events (Number) |
|---|
| number of events | number of no events |
|---|
| IV Ganciclovir | 9 | 21 |
| Placebo | 6 | 27 |
Percentage of Participants Receiving Maribavir Rescue Treatment Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 With Maintenance of Effect Through Week 16
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration NCT02931539)
Timeframe: Up to Week 16
| Intervention | percentage of participants (Number) |
|---|
| Maribavir Rescue Arm | 27.3 |
Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration NCT02931539)
Timeframe: From start of maribavir rescue treatment through 8 weeks
| Intervention | percentage of participants (Number) |
|---|
| Maribavir Rescue Arm | 50.0 |
Predose Concentration (Cmin) of Maribavir
Cmin of maribavir was reported. (NCT02931539)
Timeframe: Predose at Week 1, 4 and 8
,
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cmin at Week 1 | Cmin at Week 4 | Cmin at Week 8 |
|---|
| Maribavir 400 mg | 8.77 | 7.59 | 7.19 |
| Maribavir Rescue Arm | 8.57 | 5.75 | 5.65 |
Number of Participants With All-cause Mortality by the End of the Study
All-cause mortality was analyzed by the end of study regardless of the use of rescue treatment or alternative anti-CMV treatment. Number of participants who died during the entire study period were reported. (NCT02931539)
Timeframe: From enrollment up to end of study (approximately 44 months)
| Intervention | Participants (Count of Participants) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 13 |
| Maribavir 400 mg | 27 |
Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration NCT02931539)
Timeframe: At Week 8 through Weeks 12 and 20
,
| Intervention | percentage of participants (Number) |
|---|
| At Week 8 | At Week 12 | At Week 20 |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 23.9 | 10.3 | 9.4 |
| Maribavir 400 mg | 55.7 | 22.6 | 18.3 |
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration NCT02931539)
Timeframe: At Week 8 through Weeks 12, 16 and 20
,
| Intervention | percentage of participants (Number) |
|---|
| At Week 8 | At Week 12 | At Week 16 | At Week 20 |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 18.8 | 5.1 | 5.1 | 4.3 |
| Maribavir 400 mg | 54.9 | 22.6 | 18.7 | 18.3 |
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Serious AE was any untoward medical occurrence (whether considered to be related to study-assigned treatment or not) that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital abnormality/birth defect, or was an important medical event. TEAEs was defined as any adverse events (classified by preferred term) that had a start date on or after the first dose of study treatment or that had a start date before the date of first dose of study treatment, but increased in severity after the first dose of study treatment. (NCT02931539)
Timeframe: Baseline up to 7 days or 21 days (if cidofovir used) after the last dose of study treatment (up to Week 8)
,,
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 106 | 43 |
| Maribavir 400 mg | 228 | 90 |
| Maribavir Rescue Arm | 22 | 11 |
Number of Participants Who Had Post-baseline Resistance to Maribavir
Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had post-baseline resistance to maribavir were reported. (NCT02931539)
Timeframe: After first dose of study drug up to Week 20
,,
| Intervention | Participants (Count of Participants) |
|---|
| RASs associated with pUL97 only | RASs associated with pUL27 only | RASs associated with pUL97 and pUL27 |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 0 | 0 | 0 |
| Maribavir 400 mg | 45 | 0 | 0 |
| Maribavir Rescue Arm | 4 | 0 | 0 |
Number of Participants Who Had Maribavir CMV Resistance at Baseline
Resistance-associated amino acid substitutions (RASs) to maribavir are known to generally map to the pUL97 and pUL27 genes. Genotyping was performed to identify RASs mapping to the pUL97 and pUL27 genes. Number of participants who had maribavir CMV resistance at baseline were reported. (NCT02931539)
Timeframe: At Baseline
,,
| Intervention | Participants (Count of Participants) |
|---|
| RASs associated with pUL97 only | RASs associated with pUL27 only | RASs associated with pUL97 and pUL27 |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 3 | 0 | 0 |
| Maribavir 400 mg | 0 | 1 | 0 |
| Maribavir Rescue Arm | 1 | 0 | 0 |
Time to All Cause Mortality
The time to all-cause mortality by the end of the study participation in days was calculated. Participants who were alive at the last study follow-up (regardless of use of rescue or alternative anti-CMV treatment), withdrew from study or were lost to follow-up were censored at the date of last contact. (NCT02931539)
Timeframe: From enrollment to last serious adverse event (SAE) follow-up (approximately Week 28)
| Intervention | days (Median) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 73.0 |
| Maribavir 400 mg | 55.0 |
Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia while on study-assigned treatment period were reported. (NCT02931539)
Timeframe: Baseline up to termination of study treatment (up to Week 8)
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 4.6 |
| Maribavir 400 mg | 15.8 |
Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia while off study-assigned treatment during follow-up period were reported. (NCT02931539)
Timeframe: Termination of study treatment (Week 8) up to the End of the Study (Week 20)
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 29.2 |
| Maribavir 400 mg | 40.8 |
Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks of Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy
Recurrence of CMV viremia was defined as plasma CMV DNA concentration greater than or equal to (>=) LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the first 8 weeks of study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported. (NCT02931539)
Timeframe: At Week 8
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 12.3 |
| Maribavir 400 mg | 17.9 |
Percentage of Participants With Recurrence of CMV Viremia at Any Time on Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during at any time on study regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported. (NCT02931539)
Timeframe: Baseline up to Week 20
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 33.8 |
| Maribavir 400 mg | 56.5 |
Percentage of Participants With Recurrence of CMV Viremia During the 12 Weeks Follow-up Period Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance, regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy. Percentage of participants with recurrence of CMV viremia during the 12 weeks follow-up period regardless of whether study-assigned treatment was discontinued before 8 weeks of therapy were reported. (NCT02931539)
Timeframe: End of Week 8 up to Week 20 (12 weeks follow-up period)
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 21.5 |
| Maribavir 400 mg | 38.6 |
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with recurrence of CMV viremia during the first 8 Weeks of the treatment who completed 8 weeks of study-assigned treatment were reported. (NCT02931539)
Timeframe: Baseline up to Week 8
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 9.7 |
| Maribavir 400 mg | 15.2 |
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants with Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 20 weeks of study were reported. (NCT02931539)
Timeframe: Baseline up to Week 20
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 45.2 |
| Maribavir 400 mg | 56.1 |
Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period
Recurrence of CMV viremia was defined as plasma CMV DNA concentration >=LLOQ when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV test in 2 consecutive plasma samples at least 5 days apart, after achieving confirmed viremia clearance. Percentage of participants who completed 8 weeks of study-assigned treatment with recurrence of CMV viremia during the 12 weeks of follow-up period were reported. (NCT02931539)
Timeframe: End of Week 8 up to Week 20 (12 weeks follow-up period)
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 35.5 |
| Maribavir 400 mg | 40.9 |
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at End of Week 8, Followed by Maintenance of Treatment Effect at Week 16
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration NCT02931539)
Timeframe: Up to Week 16
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 10.3 |
| Maribavir 400 mg | 18.7 |
Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration less than (<) lower limit of quantification (LLOQ) that is, <137 International Units per milliliter (IU/mL) when assessed by COBAS® AmpliPrep/COBAS® TaqMan® CMV Test in 2 consecutive postbaseline samples, separated by at least 5 days. Percentage of participants with confirmed CMV viremia clearance at end of study Week 8 regardless of whether either study-assigned treatment was discontinued before the end of the stipulated 8 weeks of therapy, and could not have received alternative anti-CMV treatment were reported. (NCT02931539)
Timeframe: Week 8
| Intervention | percentage of participants (Number) |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 23.9 |
| Maribavir 400 mg | 55.7 |
Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment
Confirmed CMV viremia clearance was defined as plasma CMV DNA concentration NCT02931539)
Timeframe: At Week 8 through Weeks 12, 16 and 20
,
| Intervention | percentage of participants (Number) |
|---|
| At Week 8 | At Week 12 | At Week 16 | At Week 20 |
|---|
| Investigator-assigned Anti-CMV Treatment (IAT) | 18.8 | 5.1 | 5.1 | 4.3 |
| Maribavir 400 mg | 54.9 | 22.6 | 18.7 | 18.3 |