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 |
| Secondary identifying numbers | RPC082 |
- 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
Not provided at time of registration
Contact information
Dr Bienvenu Sodiomon Sirima
Scientific
Scientific
Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
01 BP 2208
Ouagadougou
01
Burkina Faso
| s.sirima.cnlp@fasonet.bf |
Study information
| Study design | Open-label parallel-group multi-centre (two centres) randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient 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 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(s) | The World Health Organization (WHO)/Scientific Committee for Research In Human Subjects (SCRIHS), 19/10/2004 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Artesunate, amodiaquine |
| Primary outcome measure | 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 study start date | 01/10/2004 |
| Overall study end date | 28/02/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Months |
| Upper age limit | 5 Years |
| Sex | Both |
| Target number of participants | 750 for efficacy/safety study; 140 for study with PK (total: 890 participants) |
| 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 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
Study participating centre
Centre National de Recherche et de Formation sur le Paludisme (CNRFP)
Ouagadougou
01
Burkina Faso
01
Burkina Faso
Sponsor information
Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Research organisation
Research organisation
15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland
| Phone | +41 (0)22 906 9230 |
|---|---|
| dndi@dndi.org | |
| Website | http://www.dndi.org/ |
"ROR" |
https://ror.org/022mz6y25 |
Funders
Funder type
Research organisation
Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
No information available
Ministerie van Buitenlandse Zaken
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- Dutch Ministry of Foreign Affairs, Ministry of Foreign Affairs, Ministry of Foreign Affairs of the Kingdom of the Netherlands
- Location
- Netherlands
Medecins Sans Frontieres (MSF) (International)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | 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 |
Editorial Notes
28/03/2017: Publication references added.
