Evaluation of 4 Artemisinin-based Combinations for Treating Uncomplicated Malaria in African Children

NCT ID: NCT00393679

Last Updated: 2014-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2009-12-31

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.

Conditions

Fever; Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

AS-AQ

Group Type: EXPERIMENTAL

amodiaquine-artesunate (ASAQ)

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

dihydroartemisinin-piperaquine (DHAPQ)

Intervention Type: DRUG

DHAPQ tablets contain either 20/160mg or 40/320mg of dihydroartemisinin (DHA) and piperaquine phosphate (PQ) respectively.

3

AL

Group Type: EXPERIMENTAL

artemether-lumefantrine (AL)

Intervention Type: DRUG

Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine.

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.

Group Type: EXPERIMENTAL

Lapdap (Chlorproguanil-Dapsone) + artesunate (AS)

Intervention Type: DRUG

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.

Interventions

amodiaquine-artesunate (ASAQ)

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

Intervention Type: DRUG

dihydroartemisinin-piperaquine (DHAPQ)

DHAPQ tablets contain either 20/160mg or 40/320mg of dihydroartemisinin (DHA) and piperaquine phosphate (PQ) respectively.

Intervention Type: DRUG

artemether-lumefantrine (AL)

Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine.

Intervention Type: DRUG

Lapdap (Chlorproguanil-Dapsone) + artesunate (AS)

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.

Intervention Type: DRUG

Other Intervention Names

Coarsucam by Sanofi-Aventis; Artekin, Eurartekin by Sigma Tau; NOTE: batches expire on 31Oct08. Due to unavailability of new batches, recruitment in this arm was discontinued on 30Oct08.; Coartem, Riamet by Novartis; Lapdap by GSK.; Arsumax by Sanofi and Guilin.

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Liverpool School of Tropical Medicine

OTHER

Sponsor Role: collaborator

East African Network for Monitoring Antimalarial Treatment

NETWORK

Sponsor Role: collaborator

Centre Muraz

OTHER

Sponsor Role: collaborator

University of Calabar

OTHER

Sponsor Role: collaborator

Tropical Diseases Research Centre, Zambia

OTHER_GOV

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

Albert Schweitzer Hospital

OTHER

Sponsor Role: collaborator

Uganda Malaria Surveillance Project

OTHER

Sponsor Role: collaborator

Mbarara University of Science and Technology

OTHER

Sponsor Role: collaborator

Ministry of Health, Rwanda

OTHER_GOV

Sponsor Role: collaborator

University of Barcelona

OTHER

Sponsor Role: collaborator

Centro de Investigacao em Saude de Manhica

OTHER

Sponsor Role: collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

UmbertoC D'Alessandro, MD MsC PhD

Role: STUDY_DIRECTOR

Institute of Tropical Medicine Antwerp

Locations

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

Countries

Burkina Faso; Gabon; Mozambique; Nigeria; Rwanda; Uganda; Zambia

References

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.

Reference Type: BACKGROUND

PMID: 23217117 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22087077 (View on PubMed)

Other Identifiers

IRB Antwerp: 6/40/187

Identifier Type: -

Identifier Source: secondary_id

4 ABC

Identifier Type: -

Identifier Source: org_study_id