Low Dose Primaquine for Clearance of Gametocytes (LOPRIM)

London School of Hygiene and Tropical Medicine

Status and phase: Completed; Phase 3; Phase 2

Conditions: Plasmodium Falciparum; Malaria; Asymptomatic Malaria

Treatments: Drug: Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine; Drug: Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine; Drug: Artemether-lumefantrine combination

Study type: Interventional

Funder types: Other

Identifiers

NCT01935882

LOPRIM-1

Details and patient eligibility

About

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

Enrollment: 360 patients

Sex: All

Ages: 2 to 15 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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360 participants in 3 patient groups

Artemether-Lumefantrine

Active Comparator group

Description:

Artemether-Lumefantrine combination

Treatment:

Drug: Artemether-lumefantrine combination

Artemether-Lumefantrine-Primaquine 0.25

Experimental group

Description:

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

Treatment:

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

Artemether-Lumefantrine-Primaquine 0.4

Experimental group

Description:

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

Treatment:

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