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

January 31, 2014 updated by: Institute of Tropical Medicine, Belgium

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

Study Type

Interventional

Enrollment (Actual)

4112

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Bobo-Dioulasso, Burkina Faso
        • Centre Muraz/IRSS
      • Lambaréné, Gabon
        • Albert Schweitzer Hospital
      • Manhica, Mozambique
        • Manhiça Health Research Center
      • Calabar, Nigeria
        • Hospital
      • Kigali, Rwanda
        • Mashshesha and Rukara
      • Kampala, Uganda
        • Jinja and Tororo
      • Mbarara, Uganda
        • Mbarara,
      • Ndola, Zambia
        • Tropical Diseases Research Centre, P O Box 71769,

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 4 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Experimental: 1
AS-AQ
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
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:
  • Artekin, Eurartekin by Sigma Tau
  • NOTE: batches expire on 31Oct08. Due to unavailability of new batches, recruitment in this arm was discontinued on 30Oct08.
Experimental: 3
AL
Tablets containing 20 mg of Artemether and 120 mg of Lumefantrine.
Other Names:
  • Coartem, Riamet by Novartis
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:
  • Lapdap by GSK.
  • Arsumax by Sanofi and Guilin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PCR unadjusted treatment failure (TF28U): all treatment failures detected during the active follow up, regardless of genotyping.
Time Frame: Day 28
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.
Time Frame: Day 28
Day 28

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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.
Time Frame: Day 28
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);
Time Frame: 28 days
28 days
Hb changes day 3, 7, 14 and 28 (first and second follow up);
Time Frame: 28 days
28 days
Clinical malaria after first active follow-up;
Time Frame: 28 Days
28 Days
Clinical malaria after second active follow-up;
Time Frame: Up to seven months
Up to seven months
TF second clinical episode (D28 and D63);
Time Frame: 63 days
63 days
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).
Safety profiles including significant changes in relevant laboratory values.
Time Frame: Up to seven months
Up to seven months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

October 27, 2006

First Submitted That Met QC Criteria

October 27, 2006

First Posted (Estimate)

October 29, 2006

Study Record Updates

Last Update Posted (Estimate)

February 3, 2014

Last Update Submitted That Met QC Criteria

January 31, 2014

Last Verified

January 1, 2014

More Information

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.

Clinical Trials on Fever

Clinical Trials on amodiaquine-artesunate (ASAQ)

3
Subscribe