cgp-56697 and Severe-Acute-Malnutrition

cgp-56697 has been researched along with Severe-Acute-Malnutrition* in 4 studies

Trials

1 trial(s) available for cgp-56697 and Severe-Acute-Malnutrition

ArticleYear
A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study.
    BMC infectious diseases, 2015, Jun-12, Volume: 15

    Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded. Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking. The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.. In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded. Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program. Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons.. This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children.. ClinicalTrials.gov: NCT01958905.

    Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child, Preschool; Drug Combinations; Ethanolamines; Female; Fluorenes; Humans; Infant; Malaria, Falciparum; Male; Mali; Niger; Recurrence; Research Design; Severe Acute Malnutrition; Treatment Outcome

2015

Other Studies

3 other study(ies) available for cgp-56697 and Severe-Acute-Malnutrition

ArticleYear
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.
    Clinical pharmacology and therapeutics, 2019, Volume: 106, Issue:6

    Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub-Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic (PK)-pharmacodynamic study included 131 SAM and 266 non-SAM children administered artemether-lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit-absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the PK model. Mid-upper arm circumference was associated with decreased absorption of lumefantrine (25.4% decreased absorption per 1 cm reduction). Risk of recurrent malaria episodes (i.e., reinfection) were characterized by an interval-censored time-to-event model with a sigmoid maximum-effect model describing the effect of lumefantrine. SAM children were at risk of underexposure to lumefantrine and an increased risk of malaria reinfection compared with well-nourished children. Research on optimized regimens should be considered for malaria treatment in malnourished children.

    Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Child, Preschool; Female; Humans; Infant; Lumefantrine; Malaria, Falciparum; Male; Recurrence; Severe Acute Malnutrition

2019
Malaria and Nutritional Status Among Children With Severe Acute Malnutrition in Niger: A Prospective Cohort Study.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018, 09-14, Volume: 67, Issue:7

    The relationship between malaria infection and nutritional status is complex. Previous studies suggest malaria may increase the incidence and severity of malnutrition, while malnutrition may increase the risk of malaria infection. Here, we report bidirectional associations between malaria and nutritional status among children with uncomplicated severe acute malnutrition (SAM).. This study is a secondary analysis of a randomized, controlled trial for the treatment of uncomplicated SAM in Niger. Children aged 6-59 months were enrolled and followed for 12 weeks. Malaria infection was assessed using an histidine-rich protein 2 (HRP2) rapid diagnostic test at admission and at any follow-up visit with fever. We assessed the association of nutritional status at admission on malaria incidence using Cox proportional hazards regression and malaria infection at admission on nutritional recovery and weight and height gain using linear regression.. Of 2399 children included in the analysis, 1327 (55.3%) were infected with malaria at admission. Malaria incidence was 12.1 cases/100 person-months among those without malaria infection at admission. Nutritional status at admission was not associated with malaria incidence. Children with malaria infection at admission and subsequently treated with an artemisinin-based combination therapy had increased weight gain (0.38 g/kg/day; 95% confidence interval [CI], 0.07 to 0.69) and reduced height gain (-0.002 mm/day; 95% CI, -0.004 to -0.0008).. Malaria infection was common among children treated for uncomplicated SAM. Malaria infection may impair height gain. Proper medical and nutritional management should be ensured to prevent adverse effects of malaria infection.. NCT01613547.

    Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Child Nutrition Disorders; Child, Preschool; Cohort Studies; Female; Humans; Infant; Infant Nutrition Disorders; Malaria; Male; Niger; Nutritional Status; Prospective Studies; Severe Acute Malnutrition

2018
Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger.
    BMC medicine, 2016, 10-24, Volume: 14, Issue:1

    Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without.. Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7.. A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8-100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04-4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049).. This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7.. ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.

    Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Child, Preschool; Drug Combinations; Ethanolamines; Female; Fluorenes; Humans; Infant; Malaria, Falciparum; Male; Mali; Niger; Severe Acute Malnutrition

2016