Safety and Efficacy of Methylene Blue Combined With Artesunate or Amodiaquine for Malaria Treatment in Children of Burkina Faso: a Pilot Study

Study Overview
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Brief Summary
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The primary objective of this trial is to study the safety of the combination methylene blue (MB)-artesunate (AS) and MB-amodiaquine (AQ) in treating malaria among children compared to the safety of an AS-AQ regimen. The secondary objective is to investigate the efficacy of MB-AS and MB-AQ.

Detailed Description
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Objectives: The primary objective of this trial is to study the safety of the combination methylene blue (MB)-artesunate (AS) and MB-amodiaquine (AQ) given over three days in 6-10 year old children with uncomplicated falciparum malaria in a malaria endemic area compared to the safety of a three days AS-AQ regimen. Secondary objectives are to investigate the efficacy of MB-AS and MB-AQ. Population: Children aged 6-10 years with uncomplicated malaria from Nouna town. Sample size: N= 180 (n=60 for each group). Treatment: The participants in the MB-AS group will receive orally twice daily 9mg/kg MB combined with once daily 4mg/kg AS over 3 days. The participants in the MB-AQ group will receive orally twice daily 9mg/kg MB combined with once daily 10mg/kg AQ over 3 days. The participants of the comparator group will receive a 3 day regimen of once daily oral AS (4mg/kg) combined with once daily AQ (10mg/kg). Endpoints: The primary endpoint is the number of adverse events (AE) after drug intake until day 28. Secondary endpoints are the number of serious adverse events (SAE), adequate clinical and parasitological response (ACPR) rate on day 28, clinical and parasitological failure rates on day 3, 7, 14 and 28, changes in haematocrit until day 28, and fever and parasite clearance time.

Conditions
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Malaria

Intervention / Treatment
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* Drug: Methylene blue
* Drug: Artesunate
* Drug: Amodiaquine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 6-10 year old children Ability to swallow tablets Uncomplicated malaria caused by P. falciparum Asexual parasites ≥ 2000/µl and < 200000/µl Axillary temperature ≥ 37.5°C Burkinabe nationality Informed consent Exclusion Criteria: Complicated or severe malaria Any apparent significant disease Anaemia (haematocrit < 21%) Treated in the same trial before Antimalarial treatment prior to inclusion (last three days), except children having been treated with chloroquine

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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All

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

| Intervention/Treatment |
| --- |
|Drug: Methylene blue|nan|
|Drug: Artesunate|nan|
|Drug: Amodiaquine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of observed and self-reported non-serious adverse events over the 28 days observation period (definition chapter 11) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse events (definition: chapter 11) over the 28 days observation period |  |  | 
| ACPR rate until D28 |  |  | 
| Early treatment failure (ETF) rate |  |  | 
| Late clinical failure (LCF) rate at D14 and D28 |  |  | 
| Late parasitological failure (LPF) rate at D14 and D28 |  |  | 
| Fever clearance time |  |  | 
| Parasite clearance time |  |  | 
| Change in haematocrit after 2, 3, 7, 14 and 28 days compared to baseline |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Africa, Methalyne-blue, Artesunate, Amodiaquine