Methylene Blue Against Falciparum Malaria in Burkina Faso

NCT ID: NCT02851108

Last Updated: 2020-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2017-02-28

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.

Conditions

Malaria, Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AS-AQ-MB

Once daily a fixed dose artesunate-amodiaquine formulation combined with once daily methylene blue (15 mg/kg) over a three days period.

Group Type: EXPERIMENTAL

Methylene Blue

Intervention Type: DRUG

50 patients will receive methylene blue

AS-AQ-PQ

Once daily a fixed dose artesunate-amodiaquine over three days combined with a single dose of primaquine on day 2 (0.25 mg/kg).

Group Type: ACTIVE_COMPARATOR

Primaquine

Intervention Type: DRUG

50 patients will receive primaquine

Interventions

Methylene Blue

50 patients will receive methylene blue

Intervention Type: DRUG

Primaquine

50 patients will receive primaquine

Intervention Type: DRUG

Other Intervention Names

3,7-bis(Dimethylamino)-phenothiazine-5-ium chloride; (±)-N4-(6-Methoxychinolin-8-yl)pentan-1,4-diamine

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)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre de Recherche en Sante de Nouna, Burkina Faso

OTHER_GOV

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Olaf Mueller

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Olaf Müller, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Heidelberg University

Locations

CRSN

Nouna, , Burkina Faso

Countries

Burkina Faso

References

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.

Reference Type: DERIVED

PMID: 31600221 (View on PubMed)

Other Identifiers

UniHD008

Identifier Type: -

Identifier Source: org_study_id