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

• Register: ISRCTN
• Last refreshed on: 24 April 2017
• Main ID: ISRCTN40020296
• Date of registration: 09/10/2008
• Prospective Registration: No
• Primary sponsor: Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
• Public 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
• 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
• Date of first enrolment: 29/09/2008
• Target sample size: 1000
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN40020296
• Study type: Interventional
• Study design: Randomised single-blind two-armed single-centre comparative study (Treatment)
• Phase: Not Applicable

Countries of recruitment

Liberia

Contacts

• Name: Richard Smith

Key inclusion & exclusion criteria

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
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Malaria
Infections and Infestations
Plasmodium falciparum malaria

Intervention(s)

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).

Primary Outcome(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.

Secondary Outcome(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

Secondary ID(s)

7071

Source(s) of Monetary Support

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)