Title: Efficacy and safety of artesunate-amodiaquine combined with methylene blue for falciparum malaria treatment in African children: randomised controlled trial.

Design: Mono-centre, two arms, open randomized controlled study in children with uncomplicated falciparum malaria in Burkina Faso.

Phase: Phase II.

Objectives: The primary objective of this trial is to study the efficacy and safety of the triple therapy artesunate (AS) - amodiaquine (AQ) - methylene blue (MB) given over three days in young children with uncomplicated falciparum malaria in Burkina Faso compared to the local standard three days artemisinin-based combination therapy (ACT) AS-AQ regimen.

Population: Children aged 6-59 months with uncomplicated falciparum malaria from Nouna Hospital in north-western Burkina Faso.

Sample size: 180 patients (90 per study arm).

Inclusion Criteria:

• 6-59 months old children (male and female)
• Weight ≥ 6kg
• Uncomplicated malaria caused by P. falciparum
• Asexual parasites ≥ 2 000/µl and ≤ 200 000/µl
• Axillary temperature ≥ 37.5°C or a history of fever during last 24 hours
• Burkinabe nationality
• Permanent residence in the study area with no intention of leaving during the surveillance period
• Informed consent

Exclusion Criteria:

• Severe malaria (WHO 2000)
• Vomiting (3 or more within 24 hours before the visit)
• Any apparent significant disease, including severe malnutrition
• A history of a previous, significant adverse reaction to either of the study drugs
• Anaemia (haemoglobin < 7 g/dl)
• Treated in the same trial before
• All modern antimalarial treatment prior to inclusion (last seven days)
• Simultaneous participation in another investigational study
• Treatment with other investigational drugs