دورية أكاديمية
أعرض في EDS

Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria.

التفاصيل البيبلوغرافية
العنوان: Chlorproguanil-dapsone-artesunate versus artemether-lumefantrine: a randomized, double-blind phase III trial in African children and adolescents with uncomplicated Plasmodium falciparum malaria.
المؤلفون: Premji Z; Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. zpremji@muhas.ac.tz, Umeh RE, Owusu-Agyei S, Esamai F, Ezedinachi EU, Oguche S, Borrmann S, Sowunmi A, Duparc S, Kirby PL, Pamba A, Kellam L, Guiguemdé R, Greenwood B, Ward SA, Winstanley PA
المصدر: PloS one [PLoS One] 2009 Aug 19; Vol. 4 (8), pp. e6682. Date of Electronic Publication: 2009 Aug 19.
نوع المنشور: Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Antimalarials/*therapeutic use , Artemisinins/*therapeutic use , Dapsone/*therapeutic use , Ethanolamines/*therapeutic use , Fluorenes/*therapeutic use , Malaria, Falciparum/*drug therapy , Proguanil/*analogs & derivatives, Adolescent ; Africa ; Artemisinins/administration & dosage ; Artesunate ; Child ; Dapsone/administration & dosage ; Double-Blind Method ; Ethanolamines/administration & dosage ; Female ; Fluorenes/administration & dosage ; Humans ; Lumefantrine ; Male ; Patient Compliance ; Proguanil/administration & dosage ; Proguanil/therapeutic use ; Treatment Outcome
مستخلص: Background: Chlorproguanil-dapsone-artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether-lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients.
Methods and Findings: The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (> or =1 to <15 years old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2:1) to receive CDA 2/2.5/4 mg/kg once daily for three days (N = 914) or six-doses of AL over three days (N = 458). Non-inferiority of CDA versus AL for efficacy was evaluated in the Day 28 per-protocol (PP) population using parasitological cure (polymerase chain reaction [PCR]-corrected). Cure rates were 94.1% (703/747) for CDA and 97.4% (369/379) for AL (treatment difference -3.3%, 95%CI -5.6, -0.9). CDA was non-inferior to AL, but there was simultaneous superiority of AL (upper 95%CI limit <0). Adequate clinical and parasitological response at Day 28 (uncorrected for reinfection) was 79% (604/765) with CDA and 83% (315/381) with AL. In patients with a G6PD-deficient genotype (94/603 [16%] hemizygous males, 22/598 [4%] homozygous females), CDA had the propensity to cause severe and clinically concerning hemoglobin decreases: the mean hemoglobin nadir was 75 g/L (95%CI 71, 79) at Day 7 versus 97 g/L (95%CI 91, 102) for AL. There were three deaths, unrelated to study medication (two with CDA, one with AL).
Conclusions: Although parasitologically effective at Day 28, the hemolytic potential of CDA in G6PD-deficient patients makes it unsuitable for use in a public health setting in Africa.
Trial Registration: ClinicalTrials.Gov NCT00344006.
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سلسلة جزيئية: ClinicalTrials.gov NCT00344006
المشرفين على المادة: 0 (Antimalarials)
0 (Artemisinins)
0 (Ethanolamines)
0 (Fluorenes)
60W3249T9M (Artesunate)
8O3249M729 (chlorproguanil)
8W5C518302 (Dapsone)
F38R0JR742 (Lumefantrine)
S61K3P7B2V (Proguanil)
تواريخ الأحداث: Date Created: 20090820 Date Completed: 20100119 Latest Revision: 20211020
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC2724683
DOI: 10.1371/journal.pone.0006682
PMID: 19690618
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0006682