Condition category
Infections and Infestations
Date applied
26/11/2007
Date assigned
29/11/2007
Last edited
28/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Bienvenu Sodiomon Sirima

ORCID ID

Contact details

Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
01 BP 2208
Ouagadougou
01
Burkina Faso
-
s.sirima.cnlp@fasonet.bf

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

RPC082

Study information

Scientific title

A randomised, controlled, open-label, parallel-group study comparing the efficacy and safety of an oral artesunate-amodiaquine fixed-dose combination therapy over 3 subsequent days to an equivalent dose regimen of the individual drugs for the treatment of children with Plasmodium falciparum

Acronym

Study hypothesis

This trial consists of two studies: the efficacy/safety study and the efficacy/safety/ PharmacoKinetic (PK) study

Primary objective (for both efficacy/safety and efficacy/safety/PK studies): To show the non-inferiority in terms of efficacy of the fixed combination AmodiaQuine (AQ)/ArteSunate (AS) compared to both drugs taken separately

Secondary objectives:
1. To evaluate treatment tolerability and safety in all participants (890 patients)
2. To evaluate the PK of AS and AQ in 140 patients

Ethics approval

The World Health Organization (WHO)/Scientific Committee for Research In Human Subjects (SCRIHS), 19/10/2004

Study design

Open-label parallel-group multi-centre (two centres) randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Malaria

Intervention

The overall trial start and end dates above refer to the efficacy/safety study. The overall trial start and end dates of the study with PK are September 2006 and December 2006, respectively.

Patients will be equally randomized into the following treatment groups:
1. Fixed dose AS/AQ combination - Tablets containing 25 mg AS and 67.5 mg AQ, 1 tablet per day for children aged 0-11 months; 2 tablets per day for children aged 1-5.
2. AS (50 mg) + AQ (153 mg). 1/2 AS tablet and 1/2 AQ tablet per day for children aged 0-11 months; 1 AS tablet and 1 AQ tablet per day for children aged 1-5 years.

Duration of treatment: 3 consecutive days

Intervention type

Drug

Phase

Not Applicable

Drug names

Artesunate, amodiaquine

Primary outcome measures

To show the non-inferiority in terms of efficacy of the fixed-dose combination AQ/AS compared to both drugs given separately. Efficacy will be measured by:
1. Cure rate (elimination of parasitemia without relapse) 28 days after the beginning of treatment
2. Parasitemia reduction rate and parasite clearance time (Duration of follow-up: 28 days)
3. Fever clearance time (Duration of follow-up: 28 days)
4. Gametocyte carrier rate (Duration of follow-up: 28 days)

Secondary outcome measures

Tolerance and safety. The following will be evaluated at each visit until day 28 (Day 0, 1, 2, 3, 7, 14, 21 and 28):
1. Clinical tolerance and safety, measured by the following:
1.1. Signs/symptoms which may appear after the treatment
1.2. Serious adverse events
1.3. In study with PK only: ElectroCardioGram (ECG) anomalies (prolonged QT interval). Measured at day 0, 2 and 28

2. Biological tolerance and safety. The following will be measured by blood tests at day 0, 7 and 28 (If abnormal values are found at day 7 or day 14, the measurements will also be carried out on day 14 and 21 in addition to day 28):
2.1. Biochemical tests:
a. ALanine AminoTransferase [ALAT]
b. Bilirubin
c. Creatinine
2.2. Hematological tests:
a. Complete Blood Count [CBC]

3. In study with PK only: PK parameters (Population PK, AUC, Cmax, Tmax, T1/2)

Overall trial start date

01/10/2004

Overall trial end date

28/02/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patient between 6 months and <5 years old
2. Bodyweight >= 5 kg (to help the assay of artesunate)
3. P. falciparum single-species infection with positive parasitemia (asexual forms) greater than 1,000 parasites per microlitre of blood
4. Fever (uncorrected axillary temperature >37.5°C) on Day 0 in children
5. No other obvious cause for the fever (e.g., respiratory [ear, nose and/or throat] infection)
6. Consent of the child's family or guardian

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

750 for efficacy/safety study; 140 for study with PK (total: 890 participants)

Participant exclusion criteria

1. Signs of life threatening and/or severe malaria
2. Other underlying diseases (cardiac, renal, hepatic, severe malnutrition)
3. Allergy to the study drugs
4. Treatment with amodiaquine within the past 7 days, or with artemisinin derivatives within the past 3 days (72 h)
5. Complete cure with an antimalarial within the past 7 days (with the exception of chloroquine)
6. On-going treatment with an antibiotic with antimalarial action (e.g. co-trimoxazole, tetracycline, or macrolide)

Recruitment start date

01/10/2004

Recruitment end date

28/02/2006

Locations

Countries of recruitment

Burkina Faso

Trial participating centre

Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
Ouagadougou
01
Burkina Faso

Sponsor information

Organisation

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Sponsor details

15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland
+41 (0)22 906 9230
dndi@dndi.org

Sponsor type

Research organisation

Website

http://www.dndi.org/

Funders

Funder type

Research organisation

Funder name

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Ministerie van Buitenlandse Zaken

Alternative name(s)

Dutch Ministry of Foreign Affairs, Ministry of Foreign Affairs, Ministry of Foreign Affairs of the Kingdom of the Netherlands

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Netherlands

Funder name

Medecins Sans Frontieres (MSF) (International)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2009 results in: https://www.ncbi.nlm.nih.gov/pubmed/19691851
2009 results in: https://www.ncbi.nlm.nih.gov/pubmed/19291301

Publication citations

Additional files

Editorial Notes

28/03/2017: Publication references added.