Evaluation of 4 Artemisinin-based Combinations for Treating Uncomplicated Malaria in African Children
Summary
The main objective is to compare the safety and efficacy of 4 artemisinin-based combinations (ACT) \[amodiaquine-artesunate (AQ+AS), dihydroartemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and chlorproguanil/dapsone plus artesunate\] for single and repeat treatments of uncomplicated malaria in children. Safety will be determined by registering adverse events and grading, laboratory, and vital signs evaluations. Their incidence will be compared between the different study arms. TO BE NOTED: following GlaxoSmithKline decision to discontinue the clinical development of the fixed-doses combination of Lapdap (Chlorproguanil-Dapsone) and artesunate, the Lapdap plus Artesunate arm was immediately discontinued in this study, on 17th February 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities. The leading EC approved the amendment on 2nd June 2008. TO BE NOTED: since the batches of the study drug DHAPQ expire at the end of October 2008, and because of the unavailability of a new batch of DHAPQ from the manufacturer, the recruitment in the DHAPQ arm had to be discontinued on 30th October 2008. A formal amendment has been submitted to all the concerned ECs and competent authorities.
Timeline
- Start
- 2007-07
- Primary completion
- 2009-12
- Completion
- 2009-12
Outcome
Mixed primary results
paper At day 28, for the PCR-adjusted efficacy, non-inferiority was established for three pair-wise comparisons: PMID 22087077 ↗
paper CD+A was significantly less efficacious than the other three treatments. PMID 22087077 ↗
Publications
- Background Ravinetto RM, Talisuna A, De Crop M, van Loen H, Menten J, Van Overmeir C, Tinto H, Gonzalez R, Meremikwu M, Nabasuma C, Ngoma GM, Karema C, Adoke Y, Chaponda M, Van Geertruyden JP, D'Alessandro U. Challenges of non-commercial multicentre North-South collaborative clinical trials. Trop Med Int Health. 2013 Feb;18(2):237-41. doi: 10.1111/tmi.12036. Epub 2012 Dec 10.
- Results Four Artemisinin-Based Combinations (4ABC) Study Group. A head-to-head comparison of four artemisinin-based combinations for treating uncomplicated malaria in African children: a randomized trial. PLoS Med. 2011 Nov;8(11):e1001119. doi: 10.1371/journal.pmed.1001119. Epub 2011 Nov 8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | ARTENIMOL | Small molecule | 20 mg | — |
| Subject | ARTENIMOL | Small molecule | 40 mg | — |
| Subject | Artemether | Small molecule | 20 mg | — |
| Subject | Artesunate | Small molecule | 25 mg | — |
| Subject | Artesunate | Small molecule | 50 mg | — |
| Subject | Artesunate | Small molecule | 100 mg | — |
| Subject | Dapsone | Small molecule | 18.75 mg | — |
| Subject | Dapsone | Small molecule | 100 mg | — |
| Subject | amodiaquine | Other / unclassified | 67.5 mg | — |
| Subject | amodiaquine | Other / unclassified | 135 mg | — |
| Subject | amodiaquine | Other / unclassified | 270 mg | — |
| Subject | chlorproguanil | Small molecule | 15 mg | — |
| Subject | chlorproguanil | Small molecule | 80 mg | — |
| Subject | lumefantrine | Small molecule | 120 mg | — |
| Subject | piperaquine | Small molecule | 160 mg | — |
| Subject | piperaquine | Small molecule | 320 mg | — |