Clinical trial NCT02851108: Methylene Blue Against Falciparum Malaria in Burkina Faso
Official title: Safety of Artesunate-amodiaquine Combined With Methylene Blue or Primaquine for Falciparum Malaria Treatment in African Children: A Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria, Falciparum
Keywords: falciparum malaria
sub saharan
africa
elimination disorder
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Centre de Recherche en Sante de Nouna, Burkina Faso
First posted: 2016-08-01
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Haemoglobin Compared to the Baseline
timeFrame: 7 days
Secondary outcomes:
measure: Gametocyte Prevalence
timeFrame: 28 days
measure: Adverse Events (AE)
timeFrame: 28 days
measure: Mothers/Caretakers Questionnaire on Acceptance
timeFrame: 14 days
measure: Gametocyte Density
timeFrame: 28 days
Other outcomes:
Locations:
city: Nouna
country: Burkina Faso
facility: CRSN
Study officials:
affiliation: Heidelberg University
name: Olaf Müller, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mendes Jorge M, Ouermi L, Meissner P, Compaore G, Coulibaly B, Nebie E, Krisam J, Klose C, Kieser M, Jahn A, Lu G, D Alessandro U, Sie A, Mockenhaupt FP, Muller O. Safety and efficacy of artesunate-amodiaquine combined with either methylene blue or primaquine in children with falciparum malaria in Burkina Faso: A randomized controlled trial. PLoS One. 2019 Oct 10;14(10):e0222993. doi: 10.1371/journal.pone.0222993. eCollection 2019.