NIAID 379821

Trial name or title	Chloroquine alone or in combination for malaria in children in Malawi
Methods	Trial design: Open‐label, randomized, controlled trial with four treatment arms. Follow‐up: No details available. Weekly follow‐up until day 28 for episode of uncomplicated malaria. Participants can take part with more than one episode of malaria during the course of one year. They will be treated with the same regimen throughout the year. Adverse event evaluation: No details available.
Participants	Inclusion criteria: Subjects aged greater than or equal to six months to five years presenting to Ndirande Health Centre with signs or symptoms consistent with malaria including, but not limited to, one or more of the following: fever at the time of evaluation (axillary temperature greater than or equal to 37.5 ºC by digital thermometer); report of fever within the last two days; clinically‐profound anaemia (conjunctival or palmar pallor); headache; body aches; abdominal pain; decreased intake of food or fluids; weakness. Weight greater than or equal to 5kg. Positive malaria smear for P. falciparum mono‐infection with parasite density between 2,000/mm3 and 200,000/mm3. Planning to remain in the study area for one year. Willingness to return for four‐weekly routine visits, as well as unscheduled sick visits. Parental/guardian consent for each participant. Exclusion criteria: Signs of severe malaria; one or more of the following: haemoglobin less than or equal to 5 g/dL; prostration; respiratory distress; bleeding; recent seizures; coma or obtundation (Blantyre coma score < 5); inability to drink; persistent vomiting. Known allergy or history of adverse reaction to chloroquine, artesunate, azithromycin, erythromycin or atovaquone‐proguanil. Chronic medication with any antibiotic or antimalarial medication. Previous enrolment in this study. Alanine aminotransferase more than five times the upper limit of normal or creatinine greater than three times the upper limit of normal. Evidence of chronic disease or physical stigmata of severe malnutrition (i.e. loss of muscle mass or subcutaneous tissue, edema, or skin or hair findings consistent with severe malnutrition).
Interventions	arm 1) Azithromycin 30 mg/kg once a day for three days (200 mg/5cc suspension), and chloroquine 10 mg/kg on day 0 and 1, 5 mg/kg on day 2 (100 mg tablets) arm 2) Artesunate 4 mg/kg once a day for three days (50 mg tablets), and chloroquine 10 mg/kg on day 0 and 1, 5 mg/kg on day 2 (100 mg tablets) arm 3) chloroquine 10 mg/kg on day 0 and 1, 5 mg/kg on day 2 (100 mg tablets) arm 4) Atovaquone‐proguanil once a day for three days (paediatric tablet 62.5 mg/25 mg, full strength tablet 250 mg/100 mg) and chloroquine 10 mg/kg on day 0 and 1, 5 mg/kg on day 2 (100 mg tablets)
Outcomes	Outcomes which will be used in the review: Total failure by day 28 after first drug administration (secondary endpoint) Adverse events (safety of all study regimens)
Starting date	February 2007
Contact information	Professor Plowe, Dr. Laufer
Notes	Location: Ndirande Health Centre in Blantyre, Malawi Sponsor: National Institute of Allergy and Infectious Diseases