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

ISRCTN	ISRCTN07576538
DOI	https://doi.org/10.1186/ISRCTN07576538
Protocol serial number	RPC082
Sponsor	Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Funders	Drugs for Neglected Diseases initiative (DNDi) (Switzerland), Ministerie van Buitenlandse Zaken, Medecins Sans Frontieres (MSF) (International)

Submission date: 26/11/2007
Registration date: 29/11/2007
Last edited: 28/03/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Bienvenu Sodiomon Sirima
Scientific

Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
01 BP 2208
Ouagadougou
01
Burkina Faso

Email	s.sirima.cnlp@fasonet.bf

Study information

Primary study design	Interventional
Study design	Open-label parallel-group multi-centre (two centres) randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study objectives	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(s)	The World Health Organization (WHO)/Scientific Committee for Research In Human Subjects (SCRIHS), 19/10/2004
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Artesunate, amodiaquine
Primary outcome measure(s)	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)
Key secondary outcome measure(s)	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)
Completion date	28/02/2006

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	5 Years
Sex	All
Target sample size at registration	890
Key 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
Key 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)
Date of first enrolment	01/10/2004
Date of final enrolment	28/02/2006

Locations

Countries of recruitment

Burkina Faso

Study participating centre

Centre National de Recherche et de Formation sur le Paludisme (CNRFP)

Ouagadougou
01
Burkina Faso

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	16/03/2009		Yes	No
Results article	results	20/08/2009		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

28/03/2017: Publication references added.