LOPRIM: Low Dose Primaquine for Clearance of Gametocytes

• Sponsor: London School of Hygiene and Tropical Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01935882
• Collaborator: Radboud University Medical Center (Other), Centre national de recherche et de formation sur le paludisme (Other)
• Enrollment: 360
• Location: 1
• Arms: 3
• Duration (Months): 21.9
• Patients Per Site Per Month: 16.4

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Malaria; Asymptomatic Malaria; Plasmodium Falciparum	Drug: Artemether-lumefantrine combination; Drug: Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine; Drug: Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Artemether-Lumefantrine Artemether-Lumefantrine combination	Drug: Artemether-lumefantrine combination
Experimental: Artemether-Lumefantrine-Primaquine 0.25 Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine	Drug: Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine
Experimental: Artemether-Lumefantrine-Primaquine 0.4 Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine	Drug: Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine

Outcome Measures

Primary Outcome Measures

1. Gametocyte carriage [14 days during follow-up]

   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.

Secondary Outcome Measures

1. Transmission to Anopheles gambiae mosquitoes [day -1, day 3, day 7]

   Mosquito membrane feeding assays will be used to determine the proportion of infected mosquitoes and the oocyst burden in infected mosquitoes.

2. Haematological recovery [14 days during follow-up]

   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.

3. Primaquine and lumefantrine pharmacokinetics [7 days during follow-up]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 15 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age > 2 years and <15 years

2. Weight over 10kg

3. 1. falciparum parasitaemia >1,000 parasites and <200,000 parasites/µl
4. 1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre National de Recherche et de Formation sur le Paludisme	Ouagadougou		Burkina Faso

Sponsors and Collaborators

• London School of Hygiene and Tropical Medicine
• Radboud University Medical Center
• Centre national de recherche et de formation sur le paludisme

Investigators

• Principal Investigator: Alfred Tiono, PhD, MD, Centre national de recherche et de formation sur le paludisme

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: London School of Hygiene and Tropical Medicine
• ClinicalTrials.gov Identifier: NCT01935882
• Other Study ID Numbers: LOPRIM-1
• First Posted: Sep 5, 2013
• Last Update Posted: Sep 2, 2015
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Malaria; Lumefantrine; Artemether; Primaquine; Artemether, Lumefantrine Drug Combination

Study Results

No Results Posted as of Sep 2, 2015