Evaluation of 4 Artemisinin-based Combinations for Treating Uncomplicated Malaria in African Children
2 other identifiers
interventional
4,112
7 countries
8
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2007
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 27, 2006
CompletedFirst Posted
Study publicly available on registry
October 30, 2006
CompletedStudy Start
First participant enrolled
July 1, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2009
CompletedFebruary 3, 2014
January 1, 2014
2.4 years
October 27, 2006
January 31, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.
Day 28
PCR adjusted treatment failure up to day 28 (TF28A): all early failures before day 14 plus the recurrent parasitaemias detected at day 14 or later and classified by genotyping as recrudescence.
Day 28
Secondary Outcomes (11)
PCR unadjusted treatment failure up to day 63 (TF63U): TF28U plus all cases of recurrent parasitaemia (symptomatic or asymptomatic) detected between day 29 and day 63 by passive follow up, regardless of genotyping
Day 63
PCR adjusted treatment failure for the whole period of passive surveillance (TFAPS): TF28A plus all episodes of recurrent parasitaemia identified as recrudescence by genotyping.
Day 28
Fever clearance time.
Asexual parasite clearance time.
Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment (for both active follow-ups);
28 days
- +6 more secondary outcomes
Study Arms (4)
1
EXPERIMENTALAS-AQ
2
EXPERIMENTALDHAPQ 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.
3
EXPERIMENTALAL
4
EXPERIMENTALLapdap + AS 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 approval was obtained on 2nd June 2008.
Interventions
A fix-dose combination tablet containing artesunate-amodiaquine in three different dosages, to be used according to patient age and weight: 25mg/67.5mg; 50mg/135mg; 100mg/270mg
DHAPQ tablets contain either 20/160mg or 40/320mg of dihydroartemisinin (DHA) and piperaquine phosphate (PQ) respectively.
Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine.
Lapdap tablets contain 15/18.75mg or 80/100mg of Chlorproguanil Hydrochloride and Dapsone, respectively. Arsumax® tablets contain 50mg Artesunate. 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 approval was obtained on 2nd June 2008.
Eligibility Criteria
You may qualify if:
- Males and Females aged between 6 months and 59 months inclusive. In the sites where CDA is tested all recruited children will be aged between 12 months and 59 months inclusive (this arm was discontinued on 17th February 2008). This criterion applies only for the recruitment in the first follow up. For the second follow up, children having been included in the first follow up are eligible, regardless of their age.
- Body weight of 5 Kg and above.
- Microscopically confirmed, monoinfection of Plasmodium falciparum (parasitaemia ≥ 2,000/μL to 200,000/μL).
- Fever (axillary temperature at ≥ 37.5°C) or history of fever in the previous 24 hours.
- Haemoglobin value ≥ 7.0 g/dl;
- Signed (or thumb-printed whenever parents/guardians are illiterate) informed consent by the parents or guardians. Note the informed consent will be asked only at recruitment and will cover the whole period of the study, including second active follow up and passive case detection.
- Parents' or guardians' willingness and ability to comply with the study protocol for the duration of the trial.
You may not qualify if:
- Participation in any other investigational drug study (antimalarial or others) during the previous 30 days.
- Known hypersensitivity to the study drugs.
- Severe malaria.
- Danger signs: not able to drink or breast-feed, vomiting (\> twice in 24hours), recent history of convulsions (\>1 in 24h), unconscious state, unable to sit or stand.
- Presence of intercurrent illness or any condition (cardiac, renal, hepatic diseases) which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study, including known G6PD deficiency.
- Severe malnutrition (defined as weight for height \<70% of the median NCHS/WHO reference).
- Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carinii pneumonia in children born to HIV+ women.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Institute of Tropical Medicine, Belgiumlead
- Liverpool School of Tropical Medicinecollaborator
- East African Network for Monitoring Antimalarial Treatmentcollaborator
- Centre Murazcollaborator
- University of Calabarcollaborator
- Tropical Diseases Research Centre, Zambiacollaborator
- University Hospital Tuebingencollaborator
- Albert Schweitzer Hospitalcollaborator
- Uganda Malaria Surveillance Projectcollaborator
- Mbarara University of Science and Technologycollaborator
- Ministry of Health, Rwandacollaborator
- University of Barcelonacollaborator
- Centro de Investigacao em Saude de Manhicacollaborator
Study Sites (8)
Centre Muraz/IRSS
Bobo-Dioulasso, Burkina Faso
Albert Schweitzer Hospital
Lambaréné, Gabon
Manhiça Health Research Center
Manhiça, Mozambique
Hospital
Calabar, Nigeria
Mashshesha and Rukara
Kigali, Rwanda
Jinja and Tororo
Kampala, Uganda
Mbarara,
Mbarara, Uganda
Tropical Diseases Research Centre, P O Box 71769,
Ndola, Zambia
Related Publications (2)
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.
PMID: 23217117BACKGROUNDFour 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.
PMID: 22087077RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
UmbertoC D'Alessandro, MD MsC PhD
Institute of Tropical Medicine Antwerp
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 27, 2006
First Posted
October 30, 2006
Study Start
July 1, 2007
Primary Completion
December 1, 2009
Study Completion
December 1, 2009
Last Updated
February 3, 2014
Record last verified: 2014-01