Low Dose Primaquine for Clearance of Gametocytes

Malaria Clinical Trial

— LOPRIM  

Official title:

A Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of Low Dose Primaquine for Clearance of Gametocytes in Asymptomatic Individuals Infected With P. Falciparum in Burkina Faso

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01935882
• Other study ID #: LOPRIM-1
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 2, 2013
• Last updated: September 1, 2015
• Start date: September 2013
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Burkina Faso: Regulatory AuthorityUnited Kingdom: London School of Hygiene & Tropical Medicine
• Study type: Interventional

Clinical Trial Summary

Primaquine (PQ) is currently the only available drug that can clear mature transmission stages of P. falciparum parasites. PQ was previously shown to clear gametocytes that persist after artemisinin-combination therapy. However, there are safety concerns about the use of PQ at the currently recommended dose of 0.75mg/kg in individuals who are glucose-6-phosphate dehydrogenase (G6PD) deficient. PQ causes transient but significant haemolysis in G6PD deficient individuals; this side-effect is dose dependent. There are indications that a lower dosing of PQ may effectively reduce gametocyte carriage but the lowest efficacious dose for gametocyte clearance is currently unknown. Recently, the World Health Organization changed their recommendation to a low dose of primaquine, 0.25mg/kg. However, there is no direct evidence on the extent to which (low dose) PQ prevents malaria transmission to mosquitoes and what the lowest efficacious dose is.

In the current study we aim to identify the lowest efficacious dose of PQ in individuals with normal G6PD function. Children with asymptomatic malaria and normal G6PD enzyme function will be randomized to treatment with artemether-lumefantrine alone or in combination with low doses of PQ. All enrolled individuals will receive a full three-day course of AL, and will be randomized to receive a dose of primaquine or placebo with their fifth dose of AL. Efficacy will be determined based on gametocyte carriage during follow-up, measured by molecular methods. For a subset of participants with patent gametocytes, primaquine effect on infectivity to mosquitoes will be assessed by membrane feeding assays

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Years to 15 Years

Eligibility

Inclusion Criteria:

1. Age > 2 years and <15 years

2. Weight over 10kg

3. P. falciparum parasitaemia >1,000 parasites and <200,000 parasites/µl

4. P. falciparum gametocytes detected by microscopy

5. Normal G6PD enzyme function

6. Informed consent by legally acceptable representative

Exclusion Criteria:

1. Enrolled in another study

2. Fever or history of fever in the last 24 hours

3. Evidence of severe illness/ danger signs

4. Known allergy to study medications

5. Hb < 8g/dL

6. Started menstruation

7. Pregnancy or breastfeeding

8. Antimalarials taken within the last 2 days

9. Primaquine taken within the last 4 weeks

10. Blood transfusion within the last 90 days

11. Non-falciparum malaria co-infection

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asymptomatic Malaria
• Malaria
• Plasmodium Falciparum

Intervention

Drug:
• Artemether-lumefantrine combination

• Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine

• Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine

Locations

Country	Name	City	State
Burkina Faso	Centre National de Recherche et de Formation sur le Paludisme	Ouagadougou

Sponsors (3)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso, Radboud University

Country where clinical trial is conducted

Burkina Faso, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gametocyte carriage	Gametocyte prevalence at enrolment and on days 2, 3, 7, 10, 14 during follow-up.; The duration of gametocyte carriage in days will be estimated.	14 days during follow-up	No
Secondary	Transmission to Anopheles gambiae mosquitoes	Mosquito membrane feeding assays will be used to determine the proportion of infected mosquitoes and the oocyst burden in infected mosquitoes.	day -1, day 3, day 7	No
Secondary	Haematological recovery	Haemoglobin concentration will be determined at enrolment and on days 2, 3, 7, 10 and 14 during follow-up. Haemoglobin concentration will be presented as grams per decilitre and as concentration relative to enrolment value.	14 days during follow-up	Yes
Secondary	Primaquine and lumefantrine pharmacokinetics	The pharmacokinetic sampling will measure primaquine, lumefantrine and metabolites. Sampling involves 7 venous blood samples during the first 72 hours after treatment and a single later time point at day 7 post initiation of treatment. Drug plasma levels will be related to treatment arm and to the participant's Cytochrome P450 2D6 metabolizer status. CYP2D6 is an enzyme involved in primaquine metabolism.	7 days during follow-up	No