A phase IV randomised study to assess the tolerability of artesunate-amodiaquine (AS-AQ) (Winthrop® fixed dose combination [FDC]) and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia

ISRCTN	ISRCTN40020296
DOI	https://doi.org/10.1186/ISRCTN40020296
Protocol serial number	7071
Sponsor	Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Funder	Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

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

Primary study design	Interventional
Study design	Randomised single-blind two-armed single-centre comparative study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A phase IV randomised study to assess the tolerability of artesunate-amodiaquine (AS-AQ) (Winthrop® fixed dose combination [FDC]) and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Liberia
Study objectives	1. To describe clinical tolerability of a fixed dose of AS-AQ (Winthrop® FDC) in adults and children over 6 years with uncomplicated Plasmodium falciparum malaria compared to a non-AQ containing reference therapy, i.e. artemether-lumefantrine 2. To describe serious adverse and drug related adverse events occurring within 1 month of drug administration for both treatments 3. To assess efficacy of treatment at 28 days 4. To describe day 0 and day 7 blood levels of desethyl-amodiaquine and lumefantrine 5. To promote awareness of drug safety issues and pharmacovigilance amongst health-care workers 6. To evaluate the ability of this method to detect serious adverse events and other safety information in the post-registration phase
Ethics approval(s)	1. French CPP, approval on 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 (AS-AQ Winthrop®, Sanofi-Aventis): tablet strength AS/AQ 100/270 mg. Participants will be dosed according to body weight: 18 - 35.9 kg = 1 x 100/270 mg tablet once daily Greater than 36 kg = 2 x 100/270 mg tablets once daily 2. Artemether-lumefantrine (Coartem, Novartis): tablet strength A/L 20/120 mg. Participants will be dosed according to body weight: 15 - 24.9 kg = 2 x 20/120 mg tablets twice daily, 8 - 12 hour between dosages 25 - 34.9 kg = 3 x 20/120 mg tablets twice daily, 8 - 12 hour between dosages Greater than 35 kg = 4 x 20/120 mg tablets twice daily, 8 - 12 hour between dosages For both arms: 3 days of treatment + 25 follow-up days (study duration/patient = 28 days).
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Artesunate-amodiaquine (AS-AQ) (Winthrop® fixed dose combination [FDC]), artemether-lumefantrine
Primary outcome measure(s)	To describe clinical tolerability of a fixed dose of AS-AQ (Winthrop® FDC) in adults and children over 6 years with uncomplicated P. falciparum malaria compared to a non-AQ containing reference therapy, i.e. artemether-lumefantrine. The clinical tolerability will be defined as the occurrence of most common adverse events.
Key secondary outcome measure(s)	1. To describe serious adverse and drug related adverse events occurring within 1 month of drug administration for both treatment 2. To assess efficacy of treatment at 28 days (polymerase chain reaction [PCR] genotyping corrected) 3. To describe day 0 and day 7 blood levels of desethyl-amodiaquine and lumefantrine
Completion date	01/04/2009

Eligibility

Participant type(s)	Patient
Age group	Mixed
Sex	All
Target sample size at registration	1000
Key inclusion criteria	1. Aged greater than or equal to 6 years, either sex 2. Weight greater than or equal to 18 kg 3. Symptoms of malaria defined as fever (axillary temperature greater than or equal to 37.5°C), or history of fever in previous 48 hours 4. Microscopic confirmation of asexual stages of P. falciparum or mixed infection 5. Willingness to attend for follow-up 6. Signed informed consent by patient or responsible caregiver
Key exclusion criteria	1. Pregnancy (pregnancy test to be performed in women of childbearing age) 2. Severe malaria 3. AS-AQ or AL treatment at appropriate dose or more than two doses of another antimalarial in the previous 4 weeks 4. Known hypersensitivity to artemisinin derivates or amodiaquine, or artemether-lumefantrine 5. Severe anaemia (less than 5 g/dl haemoglobin) 6. Concomitant febrile illness if additional medication is required other than antipyretics
Date of first enrolment	29/09/2008
Date of final enrolment	01/04/2009

Locations

Countries of recruitment

Liberia

Study participating centre

Saclepea CHC

Nimba county
-
Liberia

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	17/07/2013		Yes	No
Results article	results	17/07/2013		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

28/03/2017: internal review.
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 31/05/2009.