Methylene Blue Against Falciparum Malaria in Burkina Faso

NCT02851108 | Completed Phase 2 Results

• 1 other identifier: UniHD008
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria, Falciparum

Keywords

falciparum malaria; sub saharan; africa; elimination disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Gametocyte Prevalence

  28 days

• Adverse Events (AE)

  28 days

• Mothers/Caretakers Questionnaire on Acceptance

  14 days

• Gametocyte Density

  28 days

Study Arms (2)

AS-AQ-MB

EXPERIMENTAL

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

AS-AQ-PQ

ACTIVE COMPARATOR

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

Interventions

Methylene Blue DRUG

50 patients will receive methylene blue

Also known as: 3,7-bis(Dimethylamino)-phenothiazine-5-ium chloride

AS-AQ-MB

Primaquine DRUG

50 patients will receive primaquine

Also known as: (±)-N4-(6-Methoxychinolin-8-yl)pentan-1,4-diamine

AS-AQ-PQ

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Heidelberg University: lead
• Centre de Recherche en Sante de Nouna, Burkina Faso: collaborator

Study Sites (1)

CRSN

Nouna, Burkina Faso

Location

Related Publications (1)

• 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.

  PMID: 31600221 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Elimination Disorders

Interventions

Methylene Blue; Primaquine

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: Prof. Dr. Olaf Müller
• Organization: Heidelberg University

olaf.mueller@urz.uni-heidelberg.de

+49 6221 56 4904

Study Officials

• Olaf Müller, Prof. Dr.

  Heidelberg University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: August 1, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: February 1, 2017
• Last Updated: March 25, 2020
• Results First Posted: March 25, 2020

Record last verified: 2020-03

Locations

BU (1)