Methylene Blue Against Falciparum Malaria in Burkina Faso

The overall goal of the underlying research project is to develop a MB-based first-line drug combination regimen against uncomplicated falciparum malaria in SSA.

The primary objective of this study is: To study the safety of the triple combination AS-AQ-MB compared to AS-AQ-PQ in the treatment of uncomplicated falciparum malaria in young African children. The secondary objective of this study is: To study the efficacy of this MB-based triple combination in comparison with standard ACT-PQ in the treatment of uncomplicated falciparum malaria in young African children.

It is a mono-center, open randomised controlled non-inferiority study in children with uncomplicated falciparum malaria in Burkina Faso. Patients will be randomised to two treatment groups (arms):

• AS-AQ-MB
• AS-AQ-PQ

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

Sample size: 100 patients (50 per study arm).

Treatment: The group AS-AQ-MB will receive once daily a fixed dose AS-AQ formulation combined with once daily MB (15 mg/kg) over a three days period. The control group will receive once daily a fixed dose AS-AQ over three days combined with a single dose of PQ on day 2 (0.25 mg/kg).

Endpoints: Primary endpoint is the haemoglobin value on day 7 compared to baseline. Secondary endpoints are adverse events (AE), adequate clinical and parasitological response (ACPR) rate (PCR-corrected for recrudescences), as well as gametocyte prevalence and density.

Inclusion criteria

• Weight ≥ 6 kg
• Uncomplicated malaria caused by P. falciparum
• Asexual parasites ≥ 2 000/µl and ≤ 100 000/µl
• Axillary temperature ≥ 37.5°C or a history of fever during the last 24 hours
• Burkinabe nationality
• Permanent residence in the study area with no intention of leaving during the surveillance period
• Written informed consent of parents or care takers

Exclusion criteria

• Severe malaria
• Mixed malaria infection
• Vomiting (>2 times within 24 hours before the visit)
• Any apparent significant disease, including severe malnutrition
• A history of a previous, significant adverse reaction or known allergy to one or more 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)
• Therapy with serotonin reuptake inhibitors (e.g. citalopram, escitalopram, fluoxetine, Paroxetine, Sertraline)
• Simultaneous participation in another investigational study
• Patients with known HIV/AIDS disease
• Therapy with drugs known to inhibit the liver enzymes cytochrome 2A6 (e.g. methoxsalen, pilocarpine, tranylcypromine) and/or cytochrome 2C8 (e.g. trimethoprim, ketoconazole, ritonavir, saquinavir, lopinavir, gemfibrozil, montelukast)