Clinical trial NCT01935882: Low Dose Primaquine for Clearance of Gametocytes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Malaria
Asymptomatic Malaria
Plasmodium Falciparum
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
name: Centre national de recherche et de formation sur le paludisme
First posted: 2013-09-05
Enrollment: 360
Sex: ALL
Minimum age (years): 2
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Gametocyte carriage
timeFrame: 14 days during follow-up
Secondary outcomes:
measure: Transmission to Anopheles gambiae mosquitoes
timeFrame: day -1, day 3, day 7
measure: Haematological recovery
timeFrame: 14 days during follow-up
measure: Primaquine and lumefantrine pharmacokinetics
timeFrame: 7 days during follow-up
Other outcomes:
Locations:
city: Ouagadougou
country: Burkina Faso
facility: Centre National de Recherche et de Formation sur le Paludisme
Study officials:
affiliation: Centre national de recherche et de formation sur le paludisme
name: Alfred Tiono, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goncalves BP, Pett H, Tiono AB, Murry D, Sirima SB, Niemi M, Bousema T, Drakeley C, Ter Heine R. Age, Weight, and CYP2D6 Genotype Are Major Determinants of Primaquine Pharmacokinetics in African Children. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02590-16. doi: 10.1128/AAC.02590-16. Print 2017 May.
citation: Goncalves BP, Tiono AB, Ouedraogo A, Guelbeogo WM, Bradley J, Nebie I, Siaka D, Lanke K, Eziefula AC, Diarra A, Pett H, Bougouma EC, Sirima SB, Drakeley C, Bousema T. Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial. BMC Med. 2016 Mar 8;14:40. doi: 10.1186/s12916-016-0581-y.