Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
7070
Study information
Scientific title
Efficacy of amodiaquine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Nimba county, Liberia
Acronym
Study hypothesis
1. To evaluate the efficacy of amodiaquine-artesunate and artemether-lumefantrine among children between 6 and 59 months old suffering from uncomplicated malaria defined as the polymerase chain reaction (PCR)-adjusted cure rates at day 42
2. To assess the safety of amodiaquine-artesunate and artemether-lumefantrine treatment among children between 6 and 59 months old suffering from uncomplicated malaria
3. To assess inter-patient absorption differences possibly influencing efficacy
4. To formulate recommendations for adapted case management in Nimba county
Ethics approval
1. French CPP, 03/07/2008
2. Liberian Ministry of Health and Social Welfare, approval on 23/09/2008
Study design
Randomised single-blind two-armed single-centre comparative study
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
Patients will be equally randomised into the following treatment groups:
1. Artesunate-amodiaquine fixed dose combination (AS/AQ FDC) (artesunate amodiaquine Winthrop® Sanofi Aventis):
1.1. Artesunate 25 mg/amodiaquine 67.5 mg 1 tablet/day for 3 days in children 5 kg to 8.9 kg
1.2. Artesunate 50 mg/amodiaquine 135 mg 1 tablet/day for 3 days in children 9 kg to 17.9 kg
1.3. Artesunate 100 mg/amodiaquine 270 mg 1 tablet/day for 3 days in children 18 kg to 35.9 kg
2. Coartem®: artemether 20 mg - lumefantrine 120 mg co-formulated tabs (Coartem®, Novartis) given as six twice-daily doses over three days:
2.1. One tablet/dose for weight 5 - 14.9 kg (total 6 tablets)
2.2. Two tablets/dose for weight 15 - 24.9 kg (total 12 tablets)
2.3. Three tablets/dose for weight 25 - 34.9 kg (total 18 tablets)
2.4. Four tablets/dose for weight greater than or equal to 35 kg (total 24 tablets)
The second dose will be given 8 to 12 hours after the first dose, given at inclusion. Patients will be given milk, or encouraged to breastfeed, before each dose is taken.
For both arms: 3 days of treatment + 39 follow-up days (study duration/patient = 42 days).
Intervention type
Drug
Phase
Not Applicable
Drug names
Amodiaquine, artesunate, artemether, lumefantrine
Primary outcome measure
1. To evaluate the efficacy of both drugs uncorrected by PCR genotyping at day 42 and to compare the re-infection rates
2. To evaluate the PCR corrected and uncorrected efficacy of amodiaquine-artesunate and artemether-lumefantrine on day 28 of follow up
Secondary outcome measures
1. To assess the safety of amodiaquine-artesunate and artemether-lumefantrine treatment among children between 6 and 59 months old suffering from uncomplicated malaria by documenting adverse events that occurred during the study, before:
1.1. Day 28
1.2. Day 42
1.3. By documenting serious adverse events (SAE)
2. To assess inter patient absorption differences possibly influencing efficacy by measuring the pharmacokinetic (PK) of amodiaquine and lumefantrine at day 0 and day 7
Overall trial start date
17/11/2008
Overall trial end date
01/07/2009
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age group of 6 and 59 months, either sex
2. Weight greater than or equal to 5 kg
3. Slide-confirmed infection with Plasmodium falciparum only (no mixed infections)
4. Asexual parasite density between 2,000 and 200,000/µl of blood, and
5. Measured axillary temperature greater than or equal to 37.5°C or history of fever in the last 48 hours, and
6. High probability of respecting the follow-up visits (residence within 1 hour walking distance from the OPD, no upcoming travel plans, etc.), and
7. Informed consent from a parent or guardian aged at least 18 years
Participant type
Patient
Age group
Mixed
Gender
Both
Target number of participants
300
Participant exclusion criteria
1. General danger signs according to the World Health Organization (WHO) definition
2. Signs of severe/complicated malaria according to the WHO definition
3. Severe anaemia (haemoglobin less than 5 g/dL)
4. Known history of hypersensitivity to any of the study drugs
5. Severe malnutrition (as defined by a weight-for-height below 70% of median and/or symmetrical oedemas involving at least the feet)
6. Concomitant febrile illness judged as due to causes other than malaria with the potential to confound study outcome (measles, acute lower tract respiratory infection, otitis media, tonsillitis, abscesses, severe diarrhoea with dehydration, etc; mild flu shouldn't lead to exclusion)
7. Having received already a full course of the treatment (or one of the treatments) under study in the previous 10 days
Recruitment start date
17/11/2008
Recruitment end date
01/07/2009
Locations
Countries of recruitment
Liberia
Trial participating centre
Saclepea CHC
Nimba county
-
Liberia
Sponsor information
Organisation
Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Sponsor details
15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
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
Basic results (scientific)
Publication list
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23866774
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23866736
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27596849
Publication citations
-
Results
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, Pinoges L, Dhorda M, Boum Y, Sundaygar T, Zolia YM, Jones JJ, Comte E, Houzé P, Jullien V, Carn G, Kiechel JR, Ashley EA, Guérin PJ, Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial., Malar. J., 2013, 12, 251, doi: 10.1186/1475-2875-12-251.
-
Results
Schramm B, Valeh P, Baudin E, Mazinda CS, Smith R, Pinoges L, Sundaygar T, Zolia YM, Jones JJ, Comte E, Bruneel A, Branger M, Jullien V, Carn G, Kiechel JR, Ashley EA, Guérin PJ, Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria: two open-label, randomized trials in Nimba County, Liberia, Malar J, 2013 , 12, 250, doi: 10.1186/1475-2875-12-250.
-
Results
Otienoburu SD, Maïga-Ascofaré O, Schramm B, Jullien V, Jones JJ, Zolia YM, Houzé P, Ashley EA, Kiechel JR, Guérin PJ, Le Bras J, Houzé S, Selection of Plasmodium falciparum pfcrt and pfmdr1 polymorphisms after treatment with artesunate-amodiaquine fixed dose combination or artemether-lumefantrine in Liberia, Malar J, 2016 , 15, 452, doi: 10.1186/s12936-016-1503-3.