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

Plasmodium Falciparum Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02090036
• Other study ID #: 1.0.2014
• Status: Completed
• Phase: Phase 4
• First received: March 16, 2014
• Last updated: December 5, 2014
• Start date: July 2014
• Est. completion date: November 2014

Study information

• Verified date: December 2014
• Source: Muhimbili University of Health and Allied Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Tanzania: National Institute for Medical Research
• Study type: Interventional

Clinical Trial 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.

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..

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Malaria
• Plasmodium Falciparum

Intervention

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.
• 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.

Locations

Country	Name	City	State
Tanzania	Muhimbili University of Health and Allied Sciences	Dar es Salaam

Sponsors (2)

Lead Sponsor	Collaborator
Muhimbili University of Health and Allied Sciences	Karolinska Institutet

Country where clinical trial is conducted

Tanzania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of patients with urine color change score = 5 using Hillmen Urine Colour Chart, per treatment arm.		28 days.	Yes
Primary	Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA).		14 days	No
Secondary	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.	Yes