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Methylene Blue Against Falciparum Malaria in Burkina Faso (BlueACTn)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02851108
Recruitment Status : Completed
First Posted : August 1, 2016
Results First Posted : March 25, 2020
Last Update Posted : March 25, 2020
Sponsor:
Collaborator:
Centre de Recherche en Sante de Nouna, Burkina Faso
Information provided by (Responsible Party):
Olaf Mueller, Heidelberg University

Tracking Information
First Submitted Date  ICMJE June 28, 2016
First Posted Date  ICMJE August 1, 2016
Results First Submitted Date  ICMJE March 11, 2020
Results First Posted Date  ICMJE March 25, 2020
Last Update Posted Date March 25, 2020
Actual Study Start Date  ICMJE October 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
Change in Haemoglobin Compared to the Baseline [ Time Frame: 7 days ]
Haemoglobin concentrations will be measured in the field using a HemoCue® (HemoCue® AB, Angelholm, Sweden)
Original Primary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
Change in Haemoglobin Compared to the Baseline [ Time Frame: 7 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2020)
  • Gametocyte Prevalence [ Time Frame: 28 days ]
    measured microscopically at baseline and on day 1, 2, 3, 7, 14, and 28 of follow-up
  • Adverse Events (AE) [ Time Frame: 28 days ]
    Reports of observed or self-reported adverse event
  • Mothers/Caretakers Questionnaire on Acceptance [ Time Frame: 14 days ]
    Acceptance of the different treatment regimens by mothers/caretakers
  • Gametocyte Density [ Time Frame: 28 days ]
    measured microscopically at baseline and on day 1, 2, 3, 7, 14, and 28 of follow-up
Original Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • Gametocyte Prevalence [ Time Frame: 28 days ]
  • Adverse Events (AE) [ Time Frame: 28 days ]
  • Mothers/Caretakers Questionnaire on Acceptance [ Time Frame: 14 days ]
  • Gametocyte Density [ Time Frame: 28 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Methylene Blue Against Falciparum Malaria in Burkina Faso
Official Title  ICMJE Safety of Artesunate-amodiaquine Combined With Methylene Blue or Primaquine for Falciparum Malaria Treatment in African Children: A Randomised Controlled Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malaria, Falciparum
Intervention  ICMJE
  • Drug: Methylene Blue
    50 patients will receive methylene blue
    Other Name: 3,7-bis(Dimethylamino)-phenothiazine-5-ium chloride
  • Drug: Primaquine
    50 patients will receive primaquine
    Other Name: (±)-N4-(6-Methoxychinolin-8-yl)pentan-1,4-diamine
Study Arms  ICMJE
  • Experimental: 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.
    Intervention: Drug: Methylene Blue
  • Active Comparator: 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).
    Intervention: Drug: Primaquine
Publications * Mendes Jorge M, Ouermi L, Meissner P, Compaoré G, Coulibaly B, Nebie E, Krisam J, Klose C, Kieser M, Jahn A, Lu G, D Alessandro U, Sié A, Mockenhaupt FP, Müller 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 29, 2016)
100
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2017
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 59 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Burkina Faso
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02851108
Other Study ID Numbers  ICMJE UniHD008
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Olaf Mueller, Heidelberg University
Study Sponsor  ICMJE Heidelberg University
Collaborators  ICMJE Centre de Recherche en Sante de Nouna, Burkina Faso
Investigators  ICMJE
Principal Investigator: Olaf Müller, Prof. Dr. Heidelberg University
PRS Account Heidelberg University
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP