Clinical trial NCT02090036: Efficacy and Safety of a Single Low-dose Primaquine for the Clearance of Gametocytes
Official title: Efficacy and Safety of a Single Low-dose Primaquine Added to Standard Artemether-lumefantrine Treatment for the Clearance of Plasmodium Falciparum Gametocytes.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Plasmodium Falciparum
Keywords: Efficacy
Safety
Primaquine
Artemether-lumefantrine
Gametocytes
Lead sponsor: Muhimbili University of Health and Allied Sciences
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
First posted: 2014-03-18
Enrollment: 220
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess efficacy and safety of a single low-dose Primaquine added to standard artemether/lumefantrine treatment for the clearance of Plasmodium falciparum gametocytes among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status.

Detailed description: The current gained successes in malaria control are accredited partly to the availability of efficacious and fast acting artemisinins which are also potent against P. falciparum young gametocytes. Nonetheless, mature gametocytes may persist after treatment, contributing to malaria transmission. Conversely, artemisinin resistance is confirmed in South-east Asia, and it may spread to Africa. New control tools have to be integrated to sustain the gained successes, further reduce transmission and curb the spread of resistance.

Primaquine has strong gametocytocidal effect against mature gametocytes and when added to schizonticidal drugs such as artemether-lumefantrine (AL), it rapidly shorten gametocytes carriage duration, halting disease transmission. Nonetheless, its wide scale use has been hampered by a dose-dependent acute hemolytic anemia it causes in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Conversely, Artemisinins potentiate primaquine activities, thus a low dose of primaquine would be able to clear falciparum gametocytes.

The World Health Organization recommends addition of 0.25 mg/kg single-dose primaquine to Artemisinin based combination therapies in malaria endemic areas including Africa without testing for G6PD status. Nonetheless, the recommendation, relies on historical data from South-East Asia and among African Americans in the United States. Therefore, this study plans to assess safety and efficacy of 0.25 mg/kg single-dose primaquine added to a standard AL treatment against P. falciparum gametocytes clearance among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status..

Eligibility criteria: Inclusion Criteria:

* Age of 1 year and above and neither pregnant nor breast feeding.
* Weight over 10 kg.
* Body temperature ≥37.5°C) or history of fever in the last 24 hours.
* P. falciparum mono-infection.

Exclusion Criteria:

* Evidence of severe illness malaria or danger signs.
* Known allergy to study medications.
* Hemoglobin \<8 g/dl.
* Antimalarials taken within last 2 weeks.
* Blood transfusion within last 90 days and evidence of recent use (within 14 days)of or will be taking other drugs known to cause hemolysis in G6PD deficient subjects.

Primary outcomes:
measure: Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA).
timeFrame: 14 days
Secondary outcomes:
measure: Mean maximal fall in hemoglobin (g/dl) from enrolment to day 28 of follow-up defined as mean greatest negative difference in hemoglobin per treatment arm.
timeFrame: 28 days.
Other outcomes:
measure: Proportion of patients with urine color change score ≥ 5 using Hillmen Urine Colour Chart, per treatment arm.
timeFrame: 28 days.
Locations:
city: Dar es Salaam
country: Tanzania
facility: Muhimbili University of Health and Allied Sciences
Study officials:
affiliation: Karolinska Institutet
name: Andreas Martensson, PhD
role: STUDY_DIRECTOR
References:
citation: Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.
citation: Mwaiswelo R, Ngasala B, Jovel I, Aydin-Schmidt B, Gosling R, Premji Z, Mmbando B, Bjorkman A, Martensson A. Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial. Malar J. 2016 Aug 26;15(1):435. doi: 10.1186/s12936-016-1430-3.
citation: Mwaiswelo R, Ngasala BE, Jovel I, Gosling R, Premji Z, Poirot E, Mmbando BP, Bjorkman A, Martensson A. Safety of a single low-dose of primaquine in addition to standard artemether-lumefantrine regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. Malar J. 2016 Jun 10;15:316. doi: 10.1186/s12936-016-1341-3.