The Optimal Timing Of Primaquine To Prevent Malaria Transmission After Artemisinin-Combination Therapy

Phase 4

• Conditions: Malaria Transmission
• Interventions: Drug: Artemether Lumefantrine 6 dose regimen and single dose Primaquine on day 2; Drug: Artemether Lumefantrine; Drug: Artemether Lumefantrine 6 dose regimen & single dose of Primaquine on day 0

• Registration Number: NCT01906788
• Lead Sponsor: Kilimanjaro Clinical Research Institute

Brief Summary

The investigators' Hypothesis is that "The correct timing of gametocytocidal drug in combination with an effective Artemisinin Combination Therapy can limit the infectiousness of malaria-infected individuals to less than one week after initiation of treatment"

Detailed Description

Global malaria elimination is back on the agenda, gametocytocidal drugs such as primaquine are currently advocated for use in the interventions that aim to interrupt malaria transmission and hence elimination. Mature gametocytes are responsible for malaria transmission. Artemisinin based combination therapies (ACTs) has limited effect on the young gametocytes. Primaquine is able to clear mature gametocytes that remain after treatment with ACTs. Complete clearance of mature gametocytes will depend on the ideal time primaquine is given after ACT. It is important therefore that is administered at optimal time in order to have significant impact on clearing gametocytes to interrupt malaria transmission. An additional consideration is operational administration of Primaquine and compliance both of which are likely to be enhanced if the drug is administered on the day of diagnosis.

In this study, the investigators aim to determine optimal timing of primaquine administration in addition to ACT by comparing administration on day 0 with administration on day 2.

The investigators' primary end points are gametocyte prevalence and density by microscopy and Quantitative Nucleic Acid Based Amplification (QT-NASBA) on day 14, which will be compared between the two primaquine treatment arms.

Study Timeline

• Study Start: 2013-05
• Status Verified: 2013-07
• Study First Submitted: 2013-07-20
• Study First Submitted QC: 2013-07-23
• Last Update Submitted: 2013-07-23
• Study First Posted: 2013-07-24
• Last Update Posted: 2013-07-24
• Primary Completion: 2013-10
• Study Completion: 2013-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Age 3 years - 17 years
• Residents of research area
• Willingness to come for complete scheduled follow-up.
• Uncomplicated malaria with P. falciparum mono-infection
• Axillary temperature > 37.5°C and < 39.5°C, or history of fever in previous 48 hours.
• No history of adverse reactions to study medication
• Understanding of the procedures of the study by parent or guardian and willing to participate by signing written informed consent forms

Exclusion Criteria

• Haemoglobin below 9g/dl
• Inability to take drugs orally
• Known hypersensitivity to any of the drugs given
• Reported treatment with antimalarial chemotherapy in the past 2 weeks
• Evidence of chronic disease or acute infection other than malaria
• Domicile outside the study area
• Signs of severe malaria( such as respiratory distress, altered consciousness deep breathing, anaemia)
• Participating in other malaria studies conducted in the region
• Mixed malaria parasite species infection
• Positive pregnant test by Urine (UPT) if participant is female aged above 12 years
• G6PD deficient using the fluorescence spot test

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 3	Artemether Lumefantrine 6 dose regimen and single dose Primaquine on day 2	Experimental: Artemether Lumefantrine 6 dose regimen plus single dose of Primaquine (0.75/kg) on day 2
Group 1	Artemether Lumefantrine	Active comparator: Artemether Lumefantrine 6 dose regime orally
Group 2	Artemether Lumefantrine 6 dose regimen & single dose of Primaquine on day 0	Experimental: Artemether Lumefantrine 6 dose regime Plus single dose Primaquine (0.75/kg) on day 0

Primary Outcome Measures

Name	Time	Method
Gametocyte prevalence and density by microscopy and QT-NASBA	Day 14	By microscopy and QT-NASBA techniques we will determine and compare gametocyte prevalence and density on day 14 between the Primaquine treatment 2 and 3 arms.

Secondary Outcome Measures

Name	Time	Method
Haemoglobin level	days 3, 7, 10 and 14	We will compare the level of baseline haemoglobin on days 3, 7, 10 and 14 after the start of treatment between the two Primaquine arms

Trial Locations

Locations (1)

Bagamoyo Research and Training Centre; 🇹🇿 Bagamoyo, Tanzania