epoetin-alfa and Wounds-and-Injuries

Achieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy.. Patients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge.. One hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups.. No differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.

Topics: Adult; Anemia; Critical Illness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Injections, Subcutaneous; Injury Severity Score; Male; Prospective Studies; Recombinant Proteins; Reference Values; Risk Assessment; Survival Rate; Treatment Outcome; Wounds and Injuries; Wounds, Nonpenetrating; Young Adult

A randomized, double-blind, placebo-controlled, multicenter trial (EPO-2, N = 1,302) in anemic critically ill patients demonstrated a 29-day survival benefit in the trauma subgroup receiving epoetin alfa (mortality 8.9% vs. 4.1%). A second similarly designed trial (EPO-3, N = 1,460) confirmed this survival benefit in the epoetin alfa-treated trauma cohort (mortality 6.7% vs. 3.5%). This analysis presents trauma cohort data from both trials for evaluation of the impact of baseline factors including trauma-specific variables on outcomes.. Patients received 40,000 U epoetin alfa or placebo weekly, for a total of 4 (EPO-2) or 3 (EPO-3) doses, starting on ICU day 3. Kaplan-Meier survival curves for the two groups were compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression methods were used to evaluate relationship between baseline factors and mortality.. Demographic and trauma variables at baseline were comparable. Mortality was consistently reduced by approximately 50% in both studies (EPO-2--day 29 unadjusted HR: 0.46, 95% CI: 0.24-0.89; EPO-3--day 29 unadjusted HR: 0.51, 95% CI: 0.27-0.98.). Adjusting for baseline and trauma variables had minimal effect on hazard ratios for mortality at day 29 (EPO-2--day 29 adjusted HR: 0.50, 95% CI: 0.26-0.97; EPO-3--day 29 adjusted HR: 0.38, 95% CI: 0.19-0.74) and day 140 (EPO-3--adjusted HR: 0.39, 95% CI: 0.21-0.72). In EPO-3, there appeared to be an increase in clinically relevant thrombovascular events in the epoetin alfa treated group (16.4% vs. 12.5%, RR: 1.3, 95% CI: 0.93-1.85) but not in EPO-2 (11.1% vs. 13.3%, RR: 0.84, 95% CI: 0.56-1.28).. Epoetin alfa demonstrated a survival advantage in both of the critically ill trauma patient cohorts of two prospective, randomized clinical trials, which was not affected by baseline factors including trauma-specific variables. A definitive study in trauma subjects is warranted.

Topics: Blood Transfusion; Comorbidity; Critical Illness; Double-Blind Method; Epoetin Alfa; Erythropoietin; Humans; Kaplan-Meier Estimate; Proportional Hazards Models; Recombinant Proteins; Wounds and Injuries

Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions.. In this prospective, randomized, placebo-controlled trial, we enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline.. As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (+/-SD) number of red-cell units transfused (4.5+/-4.6 units in the epoetin alfa group and 4.3+/-4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6+/-2.0 g per deciliter vs. 1.2+/-1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86).. The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events. (ClinicalTrials.gov number, NCT00091910 [ClinicalTrials.gov].).

Topics: Adult; Aged; Critical Illness; Double-Blind Method; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Intensive Care Units; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Respiration, Artificial; Thrombosis; Trauma Severity Indices; Wounds and Injuries

Topics: Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Thrombosis; Wounds and Injuries

Topics: Critical Illness; Data Interpretation, Statistical; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Recombinant Proteins; Wounds and Injuries