Background

Case management of malaria is one of the key strategies being employed in most malaria endemic areas in the world. Because Plasmodium falciparum malaria is becoming resistant to commonly used and cheap antimalarial drugs such as chloroquine (CQ), amodiaquine (AQ), and sulfadoxine-pyrimethamine (SP), new and promising anti-malaria drugs need to be optimally assessed in sites with well-characterised malariometric indices in order to make the efficacious and safe ones available to affected individuals and avert deaths.

Artemisinin Combination Therapies (ACT) have been found to be efficacious and safe, producing rapid clearance of parasites and malaria symptoms; they are very well tolerated, and are associated with very good compliance.

Objectives

Primary objective:

To evaluate the efficacy of artesunate-amodiaquine versus artemether-lumefantrine, versus artesunate-lapdap in the treatment of children 6 months to ten years with uncomplicated falciparum malaria at paediatric outpatient clinic in the Kintampo hospital.

Secondary objectives:

To evaluate the safety of artesunate-amodiaquine versus artemether-lumefantrine, versus artesunate-lapdap in the treatment of children 6 months to ten years with uncomplicated falciparum malaria at paediatric outpatient clinic in the Kintampo hospital.

To develop and strengthen competitive and sustainable clinical research capacities for GCP-compliant clinical trials evaluating new antimalarial drugs in an endemic site in Africa.

Methods

Study design

This is a randomised, open-labelled, non-inferiority drug trial. At the Kintampo district hospital, 510 paediatric outpatients with uncomplicated P. falciparum malaria and aged between 6 months and 10 years will be recruited and randomly assigned to one of the three study arms: (i) Artesunate-Amodiaquine (AS-AQ), (ii) Artemether-Lumefantrine (AR-LM), or (iii) Artesunate-lapdap (AS-LP). The classification of clinical and parasitological responses will follow the relevant WHO protocol for areas of intense transmission. Follow-up, however, will be extended beyond day 14 up to day 28 to increase the sensitivity of the in vivo test. PCR-based genotyping comparing pairs of parasite isolates from day 0 and day of asexual parasite reappearance will be used to distinguish between recrudescence and re-infection.

Progress of Study:

• Scientific Review Committee has approved of protocol
• Ethical Approval has been obtained from KHRC Institutional Ethics Committee, Ghana Health Service Ethics Review Board and Ethics Review Board of the London School of Hygiene and Tropical Medicine.
• Community and other stakeholder meetings have been held.
• Logistics and study instruments are being developed
• Recruitment started in April 2005

Funding

Gates Malaria Partnership & LSHTM

Contact: Dr.Seth Owusu-agyei