Efficacy and Safety of a Single Low-dose Primaquine for the Clearance of Gametocytes

Phase 4

Completed

• Conditions: Plasmodium Falciparum
• Interventions: Drug: Primaquine (For artemether-lumefantrine+primaquine arm); Drug: Placebo (For artemether-lumefantrine arm)

• Registration Number: NCT02090036
• Lead Sponsor: Muhimbili University of Health and Allied Sciences

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..

Study Timeline

• Study First Submitted: 2014-03-16
• Study First Submitted QC: 2014-03-16
• Study First Posted: 2014-03-18
• Study Start: 2014-07
• Primary Completion: 2014-10
• Study Completion: 2014-11
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-05
• Last Update Posted: 2014-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 220

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
artemether-lumefantrine+primaquine	Primaquine (For artemether-lumefantrine+primaquine arm)	All the recruited patients will be treated with a six doses, 3 days artemether-lumefantrine treatment regimen. However, patients randomized to the artemether-lumefantrine+primaquine arm will be given 0.25 mg/kg single-dose primaquine concomitantly with artemether-lumefantrine first dose.
artemether-lumefantrine+placebo	Placebo (For artemether-lumefantrine arm)	In the artemether-lumefantrine arm, the first dose of artemether-lumefantrine will be administered concomitantly with a single-dose placebo. A volume of normal saline will be measured based on weight bands and then will be given to patients.

Primary Outcome Measures

Name	Time	Method
Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA).	14 days

Secondary Outcome Measures

Name	Time	Method
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.	28 days.

Trial Locations

Locations (1)

Muhimbili University of Health and Allied Sciences; 🇹🇿 Dar es Salaam, Tanzania