- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00393679
Evaluation of 4 Artemisinin-based Combinations for Treating Uncomplicated Malaria in African Children
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.
Study Overview
Status
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Bobo-Dioulasso, Burkina Faso
- Centre Muraz/IRSS
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Lambaréné, Gabon
- Albert Schweitzer Hospital
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Manhica, Mozambique
- Manhiça Health Research Center
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Calabar, Nigeria
- Hospital
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Kigali, Rwanda
- Mashshesha and Rukara
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Kampala, Uganda
- Jinja and Tororo
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Mbarara, Uganda
- Mbarara,
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Ndola, Zambia
- Tropical Diseases Research Centre, P O Box 71769,
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1
AS-AQ
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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
Other Names:
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Experimental: 2
DHAPQ 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. |
DHAPQ tablets contain either 20/160mg or 40/320mg of dihydroartemisinin (DHA) and piperaquine phosphate (PQ) respectively.
Other Names:
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Experimental: 3
AL
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Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine.
Other Names:
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Experimental: 4
Lapdap + 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. |
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.
Time Frame: Day 28
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Day 28
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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.
Time Frame: Day 28
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Day 28
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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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
Time Frame: Day 63
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Day 63
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PCR adjusted treatment failure for the whole period of passive surveillance (TFAPS): TF28A plus all episodes of recurrent parasitaemia identified as recrudescence by genotyping.
Time Frame: Day 28
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Day 28
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Fever clearance time.
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Asexual parasite clearance time.
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Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment (for both active follow-ups);
Time Frame: 28 days
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28 days
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Hb changes day 3, 7, 14 and 28 (first and second follow up);
Time Frame: 28 days
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28 days
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Clinical malaria after first active follow-up;
Time Frame: 28 Days
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28 Days
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Clinical malaria after second active follow-up;
Time Frame: Up to seven months
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Up to seven months
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TF second clinical episode (D28 and D63);
Time Frame: 63 days
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63 days
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Changes in the frequency of mutations in the dihydrofolate reductase (DHFR) gene at day 0 first follow-up and day re-appearance of parasitaemia (for patients treated with CDA - NOTE that CDA arm was discontinued on 17.02.2008).
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Safety profiles including significant changes in relevant laboratory values.
Time Frame: Up to seven months
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Up to seven months
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: UmbertoC D'Alessandro, MD MsC PhD, Institute of Tropical Medicine Antwerp
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Anti-Bacterial Agents
- Leprostatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Anthelmintics
- Folic Acid Antagonists
- Schistosomicides
- Antiplatyhelmintic Agents
- Lumefantrine
- Artemether
- Dapsone
- Artesunate
- Chlorproguanil
- Artemether, Lumefantrine Drug Combination
- Piperaquine
- Amodiaquine
- Artenimol
Other Study ID Numbers
- 4 ABC
- IRB Antwerp: 6/40/187
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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