Methylene Blue Against Falciparum Malaria in Burkina Faso

Malaria, Falciparum Clinical Trial

— BlueACTn  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02851108
• Other study ID #: UniHD008
• Status: Completed
• Phase: Phase 2
• Start date: October 2016
• Est. completion date: February 2017

Study information

• Verified date: March 2020
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 59 Months

Eligibility

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)

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum

Intervention

Drug:
• Methylene Blue
50 patients will receive methylene blue
• Primaquine
50 patients will receive primaquine

Locations

Country	Name	City	State
Burkina Faso	CRSN	Nouna

Sponsors (2)

Lead Sponsor	Collaborator
Heidelberg University	Centre de Recherche en Sante de Nouna, Burkina Faso

Country where clinical trial is conducted

Burkina Faso, 

Outcome

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