Methylene Blue Against Falciparum Malaria in Burkina Faso

Phase 2

Completed

Conditions: Malaria, Falciparum

Interventions: Drug: Primaquine
Drug: Methylene Blue

Registration Number: NCT02851108

Lead Sponsor: Heidelberg University

Brief Summary: 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: 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):

1. AS-AQ-MB

2. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AS-AQ-PQ	Primaquine	Once daily a fixed dose artesunate-amodiaquine over three days combined with a single dose of primaquine on day 2 (0.25 mg/kg).
AS-AQ-MB	Methylene Blue	Once daily a fixed dose artesunate-amodiaquine formulation combined with once daily methylene blue (15 mg/kg) over a three days period.

Primary Outcome Measures

Name	Time	Method
Change in Haemoglobin Compared to the Baseline	7 days	Haemoglobin concentrations will be measured in the field using a HemoCue® (HemoCue® AB, Angelholm, Sweden)

Secondary Outcome Measures

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