Efficacy of amodiaquine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Nimba county, Liberia

ISRCTN	ISRCTN51688713
DOI	https://doi.org/10.1186/ISRCTN51688713
Secondary identifying numbers	7070

Submission date: 03/10/2008
Registration date: 09/10/2008
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 Richard Smith
Scientific

Saclepea CHC
Nimba county
-
Liberia

Study information

Study design	Randomised single-blind two-armed single-centre comparative study
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	Efficacy of amodiaquine-artesunate and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Nimba county, Liberia
Study objectives	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(s)	1. French CPP, 03/07/2008 2. Liberian Ministry of Health and Social Welfare, approval on 23/09/2008
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	17/11/2008
Completion date	01/07/2009

Eligibility

Participant type(s)	Patient
Age group	Mixed
Lower age limit	6 Months
Upper age limit	59 Months
Sex	All
Target number of participants	300
Key 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
Key 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
Date of first enrolment	17/11/2008
Date of final enrolment	01/07/2009

Locations

Countries of recruitment

Liberia

Study participating centre

Saclepea CHC

Nimba county
-
Liberia

Sponsor information

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Research organisation

15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland

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

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	Peer reviewed?	Patient-facing?
Results article	results	17/07/2013	Yes	No
Results article	results	17/07/2013	Yes	No
Results article	results	05/09/2016	Yes	No

Editorial Notes

28/03/2017: Publication reference added.
13/05/2010: This record was updated to include the actual last patient visit date; the overall trial end date at the time of registration was 30/04/2009.