Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda

June 11, 2013 updated by: London School of Hygiene and Tropical Medicine

Evaluation of the Efficacy and Safety of Primaquine for Clearance of Gametocytes in Uncomplicated Falciparum Malaria in Uganda

The purpose of this study is to evaluate the safety and efficacy of lower doses of primaquine compared to the dose recommended by the WHO for reducing P. falciparum gametocytes in the infected human host to prevent transmission of falciparum malaria to the anopheles mosquito vector.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A single dose of 0.75mg/kg primaquine base is recommended by the WHO to block transmission of falciparum malaria from infected humans to mosquitoes by clearing gametocytes. However, the optimal dose for safety and efficacy has not been evaluated. Dose-finding data is important because primaquine has a dose-dependent risk of causing haemolysis (destruction of blood cells) in pre-disposed individuals, such as those with G6PD deficiency. G6PD deficiency is most prevalent in malaria-endemic areas. Therefore, it is essential that data on primaquine's safety is available in such areas.

The investigators hypothesise that lower doses of primaquine have a lower risk of adverse effects compared to the WHO-recommended dose, but retain the transmission-blocking efficacy.

The investigators propose to test this hypothesis in a four-arm clinical trial with a non-inferiority design to evaluate the efficacy and a superiority design to evaluate the safety of the WHO dose (0.75mg/kg) and lower doses of primaquine for clearance of P. falciparum gametocytes in children in Uganda. The study will include a pharmacokinetic analysis.

Study Type

Interventional

Enrollment (Actual)

468

Phase

  • Phase 3

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

  • Uganda
    • Eastern Region
      • Jinja, Eastern Region, Uganda
        • Walukuba Health Centre IV

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 to 10 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age >/= 1 year and </= 10 years
  • Weight over 10kg
  • Fever >38 degrees C (tympanic) or history of fever in the last 24 hours
  • P. falciparum parasitaemia <500 000/µl
  • Normal G6PD enzyme function

Exclusion Criteria:

  • Enrolled in another study
  • Evidence of severe illness/ danger signs
  • Known allergy to study medications
  • Haemoglobin < 8g/dL)
  • Started menstruation
  • Pregnancy or breastfeeding
  • Primaquine taken within the last 4 weeks
  • Blood transfusion within the last 90 days
  • Non-falciparum malaria co-infection

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Non-active drug
Drug: Primaquine
Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).
Other Names:
  • primaquine phosphate
Experimental: Low dose primaquine (PQ1)
Lowest experimental dose of primaquine base: 0.1mg/kg
Drug: Primaquine
Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).
Other Names:
  • primaquine phosphate
Experimental: Intermediate dose primaquine (PQ2)
Intermediate experimental dose of primaquine base: 0.4mg/kg
Drug: Primaquine
Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).
Other Names:
  • primaquine phosphate
Active Comparator: Reference dose primaquine (PQ-R)
WHO-recommended dose of primaquine base: 0.75mg/kg
Drug: Primaquine
Single dose of oral primaquine phosphate. Comparator dose is 0.75mg/kg primaquine base. Each experimental arm is a different (reduced) dose of primaquine phosphate. Placebo contains no primaquine phosphate (non-active ingredients only).
Other Names:
  • primaquine phosphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean number of days to gametocyte clearance (gametocyte clearance time, GCT)
Time Frame: 14 days
Mean number of days per treatment arm for gametocytes to become undetectable using sub-microscopic molecular testing methods (real-time nucleic acid sequence-based amplification, QT-NASBA)and interpolated from measured data points.
14 days
Mean (+/- SD) maximal fall in Hb (g/dL) from enrollment to day 28 of follow-up
Time Frame: 28 days
Mean maximal greatest negative difference in Hb (measured by Hemocue®) from enrollment value per treatment arm over 28 days follow up
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean (+/- SD) area under the curve of gametocyte density per day during 14 days of follow-up
Time Frame: 14 days
An estimate of the area under the curve of gametocytes (measured by QT-NASBA) seen over time, averaged per day of follow up (days 0-14) and interpolated from measured data points
14 days
Requirement for blood transfusion
Time Frame: 28 days
Percentage of children receiving blood transfusion per treatment arm during days 0-28
28 days
Follow-up day of Hb nadir
Time Frame: 28 days
Mean day of follow up (day 0-28) per treatment arm of lowest Hb measurement (by Hemocue®)
28 days
Incidence of serious adverse events by sign, symptom, laboratory parameter and relationship to taking study drug
Time Frame: 28 days
Percentage (number) per treatment arm during days 0-28
28 days
Incidence of gastrointestinal symptoms after taking study drug
Time Frame: 6 days
Percentage (number) of children with gastrointestinal symptoms per treatment arm during days 2-7
6 days

Collaborators and Investigators

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

Sponsor

London School of Hygiene and Tropical Medicine

Collaborators

Wellcome Trust

Investigators

  • Principal Investigator: Alice C Eziefula, MBBS MCRP MRCPath, London School of Hygiene and Tropical Medicine

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

December 1, 2011

Primary Completion (Actual)

March 1, 2013

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

June 1, 2011

First Submitted That Met QC Criteria

June 2, 2011

First Posted (Estimate)

June 3, 2011

Study Record Updates

Last Update Posted (Estimate)

June 12, 2013

Last Update Submitted That Met QC Criteria

June 11, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PQPF912

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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