Methylene Blue Against Falciparum Malaria in Burkina Faso

Study Overview
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Brief Summary
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Safety of artesunate-amodiaquine combined with methylene blue or primaquine for falciparum malaria treatment in African children: A randomised controlled trial Elimination has become the goal of malaria programmes in an increasing number of endemic countries and regions. As resistance against artemisinin compounds has recently started to emerge in South-East Asia, there is a clear need to develop alternative malaria drug combinations. Adding another anti-malarial with a short half-life such as methylene blue to standard ACT (artemisinin-based combination therapy) could be a strategy to prevent artemisinin resistance development. Moreover, adding a gametocytocidal drug to ACT reduces the probability of transmission of P. falciparum parasites including drug-resistant parasites. Objectives: The primary objective of this trial is to investigate the safety of artesunate (AS) - amodiaquine (AQ) - methylene blue (MB) compared to AS - AQ - primaquine (PQ) in young children with uncomplicated falciparum malaria in Burkina Faso.

Detailed Description
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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.

Official Title
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Safety of Artesunate-amodiaquine Combined With Methylene Blue or Primaquine for Falciparum Malaria Treatment in African Children: A Randomised Controlled Trial

Conditions
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Malaria, Falciparum

Intervention / Treatment
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* Drug: Methylene Blue
* Drug: Primaquine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AS-AQ-MB<br>Once daily a fixed dose artesunate-amodiaquine formulation combined with once daily methylene blue (15 mg/kg) over a three days period. | Drug: Methylene Blue<br>* 50 patients will receive methylene blue<br>* Other names: 3,7-bis(Dimethylamino)-phenothiazine-5-ium chloride;|
| Active Comparator: AS-AQ-PQ<br>Once daily a fixed dose artesunate-amodiaquine over three days combined with a single dose of primaquine on day 2 (0.25 mg/kg). | Drug: Primaquine<br>* 50 patients will receive primaquine<br>* Other names: (±)-N4-(6-Methoxychinolin-8-yl)pentan-1,4-diamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Haemoglobin Compared to the Baseline | Haemoglobin concentrations will be measured in the field using a HemoCue® (HemoCue® AB, Angelholm, Sweden) | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gametocyte Prevalence | measured microscopically at baseline and on day 1, 2, 3, 7, 14, and 28 of follow-up | 28 days | 
| Adverse Events (AE) | Reports of observed or self-reported adverse event | 28 days | 
| Mothers/Caretakers Questionnaire on Acceptance | Acceptance of the different treatment regimens by mothers/caretakers | 14 days | 
| Gametocyte Density | measured microscopically at baseline and on day 1, 2, 3, 7, 14, and 28 of follow-up | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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falciparum malaria, sub saharan, africa, elimination disorder