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

December 5, 2014 updated by: Richard Mwaiswelo, Muhimbili University of Health and Allied Sciences

Efficacy and Safety of a Single Low-dose Primaquine Added to Standard Artemether-lumefantrine Treatment for the Clearance of Plasmodium Falciparum Gametocytes.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

220

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Tanzania
      • Dar es Salaam, Tanzania, 65001
        • Muhimbili University of Health and Allied Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: artemether-lumefantrine+placebo
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.
Drug: Placebo (For artemether-lumefantrine arm)
Volume of normal saline mixed with coloured fruit juice measured based on weight bands will be given orally concomitantly with first dose of artemether-lumefantrine.
Experimental: artemether-lumefantrine+primaquine
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.
Drug: Primaquine (For artemether-lumefantrine+primaquine arm)
A 0.25 mg/kg single-dose primaquine will be administered concomitantly with the first dose of artemether-lumefantrine in all patients randomized into the artemether-lumefantrine+primaquine arm.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 28 days.
28 days.

Other Outcome Measures

Outcome Measure
Time Frame
Proportion of patients with urine color change score ≥ 5 using Hillmen Urine Colour Chart, per treatment arm.
Time Frame: 28 days.
28 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Muhimbili University of Health and Allied Sciences

Collaborators

Karolinska Institutet

Investigators

  • Study Director: Andreas Martensson, PhD, Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

March 16, 2014

First Submitted That Met QC Criteria

March 16, 2014

First Posted (Estimate)

March 18, 2014

Study Record Updates

Last Update Posted (Estimate)

December 8, 2014

Last Update Submitted That Met QC Criteria

December 5, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1.0.2014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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