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Completed

NCT Number: 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.

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Key information

Conditions

Fever Body Temperature Changes Infections Malaria Mosquito-Borne Diseases Parasitic Diseases Pathological Conditions, Signs and Symptoms Protozoan Infections Signs and Symptoms Vector Borne Diseases

Age range

6 month–59 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centre Muraz/IRSS, Bobo-Dioulasso, Burkina Faso

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Amodiaquine-Artesunate (ASAQ)

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

Other names: Coarsucam by Sanofi-Aventis

dihydroartemisinin-piperaquine (DHAPQ)

Drug

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

Other names: Artekin, Eurartekin by Sigma Tau, NOTE: batches expire on 31Oct08. Due to unavailability of new batches, recruitment in this arm was discontinued on 30Oct08.

Artemether-lumefantrine (AL)

Drug

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

Other names: Coartem, Riamet by Novartis

Lapdap (Chlorproguanil-Dapsone) + artesunate (AS)

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.

Other names: Lapdap by GSK., Arsumax by Sanofi and Guilin.

Primary outcomes

  1. PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.

    Time frame: Day 28

  2. 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

Secondary outcomes

  1. 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

  2. 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

  3. Fever clearance time.

  4. Asexual parasite clearance time.

  5. Gametocytaemia (prevalence and density) at day 7, 14, 21 and 28 after treatment (for both active follow-ups);

    Time frame: 28 days

  6. Hb changes day 3, 7, 14 and 28 (first and second follow up);

    Time frame: 28 days

  7. Clinical malaria after first active follow-up;

    Time frame: 28 Days

  8. Clinical malaria after second active follow-up;

    Time frame: Up to seven months

  9. TF second clinical episode (D28 and D63);

    Time frame: 63 days

  10. 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).

  11. Safety profiles including significant changes in relevant laboratory values.

    Time frame: Up to seven months

Sponsors and collaborators

Lead sponsor

Institute of Tropical Medicine, Belgium

Other

Collaborators

  • Albert Schweitzer Hospital
  • Centre Muraz
  • Centro de Investigacao em Saude de Manhica
  • East African Network for Monitoring Antimalarial Treatment
  • Liverpool School of Tropical Medicine
  • Mbarara University of Science and Technology
  • Ministry of Health, Rwanda
  • Tropical Diseases Research Centre, Zambia
  • Uganda Malaria Surveillance Project
  • University Hospital Tuebingen
  • University of Barcelona
  • University of Calabar

Registry information

Important dates

Study start
2007
Primary completion
2009
Study completion
2009
First posted
Oct 30, 2006
Registry last updated
Feb 3, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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