Background: Clindamycin plus quinine is recommended by World Health Organization as a non-artemisinin-based antimalarial drug combination. The evidence on the efficacy of clindamycin plus quinine compared with other antimalarial drugs is scanty, outdated and inconclusive. No studies have compared the efficacy of clindamycin plus quinine with that of artemether-lumefantrine in the treatment of participants with uncomplicated falciparum malaria.

Objective: To evaluate the therapeutic efficacy and safety of oral clindamycin plus quinine vs. artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in children residing in an area of intense malaria transmission of western Kenya.

Methods: An open-label randomised controlled clinical trial will be conducted at Ahero Sub-District Hospitals between September 2012 and June 2014. Study participants will be 384 children aged < 5 years with confirmed uncomplicated falciparum malaria. The participants will be randomised in a ratio of 1:1 to receive directly observed treatment with either clindamycin plus quinine or artemether-lumefantrine. Clinical and parasitological parameters will be monitored over 28 days follow up period to evaluate drug efficacy and safety.  The primary end-point will be the proportion of participants experiencing parasitological cure within 28 days of starting treatment. We will differentiate recrudescence from re-infections by analysis of MSP₁, MSP₂ and GLURP genes. Secondary end points will include fever resolution rates, parasite clearance rates, gametocyte carriage, change in mean haemoglobin (between day 0 and day 28), frequency of molecular markers of drug resistance and incidence of adverse events. This study will provide evidence that may be useful for informing the treatment policies for patients with uncomplicated P. falciparum malaria.