Clinical trial NCT00354380: Safety and Efficacy of Methylene Blue Combined With Artesunate or Amodiaquine for Malaria Treatment in Children of Burkina Faso: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Malaria
Africa
Methalyne-blue
Artesunate
Amodiaquine
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2006-07-20
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to study the safety of the combination methylene blue (MB)-artesunate (AS) and MB-amodiaquine (AQ) in treating malaria among children compared to the safety of an AS-AQ regimen. The secondary objective is to investigate the efficacy of MB-AS and MB-AQ.

Detailed description: Objectives: The primary objective of this trial is to study the safety of the combination methylene blue (MB)-artesunate (AS) and MB-amodiaquine (AQ) given over three days in 6-10 year old children with uncomplicated falciparum malaria in a malaria endemic area compared to the safety of a three days AS-AQ regimen. Secondary objectives are to investigate the efficacy of MB-AS and MB-AQ.

Population: Children aged 6-10 years with uncomplicated malaria from Nouna town.

Sample size: N= 180 (n=60 for each group).

Treatment: The participants in the MB-AS group will receive orally twice daily 9mg/kg MB combined with once daily 4mg/kg AS over 3 days. The participants in the MB-AQ group will receive orally twice daily 9mg/kg MB combined with once daily 10mg/kg AQ over 3 days. The participants of the comparator group will receive a 3 day regimen of once daily oral AS (4mg/kg) combined with once daily AQ (10mg/kg).

Endpoints: The primary endpoint is the number of adverse events (AE) after drug intake until day 28. Secondary endpoints are the number of serious adverse events (SAE), adequate clinical and parasitological response (ACPR) rate on day 28, clinical and parasitological failure rates on day 3, 7, 14 and 28, changes in haematocrit until day 28, and fever and parasite clearance time.

Eligibility criteria: Inclusion criteria:

* 6-10 year old children
* Ability to swallow tablets
* Uncomplicated malaria caused by P. falciparum
* Asexual parasites ≥ 2000/µl and \< 200000/µl
* Axillary temperature ≥ 37.5°C
* Burkinabe nationality
* Informed consent

Exclusion Criteria:

* Complicated or severe malaria
* Any apparent significant disease
* Anaemia (haematocrit \< 21%)
* Treated in the same trial before
* Antimalarial treatment prior to inclusion (last three days), except children having been treated with chloroquine

Primary outcomes:
measure: Incidence of observed and self-reported non-serious adverse events over the 28 days observation period (definition chapter 11)
Secondary outcomes:
measure: Incidence of serious adverse events (definition: chapter 11) over the 28 days observation period
measure: ACPR rate until D28
measure: Early treatment failure (ETF) rate
measure: Late clinical failure (LCF) rate at D14 and D28
measure: Late parasitological failure (LPF) rate at D14 and D28
measure: Fever clearance time
measure: Parasite clearance time
measure: Change in haematocrit after 2, 3, 7, 14 and 28 days compared to baseline
Other outcomes:
Locations:
city: Nouna
country: Burkina Faso
facility: Nouna District Hospital
Study officials:
affiliation: Heidelberg University
name: Olaf Mueller, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Heidelberg University
name: Peter Meissner, MD, MSc Trop Paed
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coulibaly B, Zoungrana A, Mockenhaupt FP, Schirmer RH, Klose C, Mansmann U, Meissner PE, Muller O. Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial. PLoS One. 2009;4(5):e5318. doi: 10.1371/journal.pone.0005318. Epub 2009 May 5.
citation: Zoungrana A, Coulibaly B, Sie A, Walter-Sack I, Mockenhaupt FP, Kouyate B, Schirmer RH, Klose C, Mansmann U, Meissner P, Muller O. Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS One. 2008 Feb 20;3(2):e1630. doi: 10.1371/journal.pone.0001630.