Low Dose Primaquine for Clearance of Gametocytes
LOPRIM
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
1 other identifier
interventional
360
1 country
1
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2013
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2013
CompletedFirst Submitted
Initial submission to the registry
September 2, 2013
CompletedFirst Posted
Study publicly available on registry
September 5, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedSeptember 2, 2015
September 1, 2015
1.8 years
September 2, 2013
September 1, 2015
Conditions
Outcome Measures
Primary Outcomes (1)
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
Secondary Outcomes (3)
Transmission to Anopheles gambiae mosquitoes
day -1, day 3, day 7
Haematological recovery
14 days during follow-up
Primaquine and lumefantrine pharmacokinetics
7 days during follow-up
Study Arms (3)
Artemether-Lumefantrine
ACTIVE COMPARATORArtemether-Lumefantrine combination
Artemether-Lumefantrine-Primaquine 0.25
EXPERIMENTALArtemether-Lumefantrine with a single dose of 0.25mg/kg primaquine
Artemether-Lumefantrine-Primaquine 0.4
EXPERIMENTALArtemether-Lumefantrine with a single dose of 0.4mg/kg primaquine
Interventions
Eligibility Criteria
You may qualify if:
- Age \> 2 years and \<15 years
- Weight over 10kg
- P. falciparum parasitaemia \>1,000 parasites and \<200,000 parasites/µl
- P. falciparum gametocytes detected by microscopy
- Normal G6PD enzyme function
- Informed consent by legally acceptable representative
You may not qualify if:
- Enrolled in another study
- Fever or history of fever in the last 24 hours
- Evidence of severe illness/ danger signs
- Known allergy to study medications
- Hb \< 8g/dL
- Started menstruation
- Pregnancy or breastfeeding
- Antimalarials taken within the last 2 days
- Primaquine taken within the last 4 weeks
- Blood transfusion within the last 90 days
- Non-falciparum malaria co-infection
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Centre National de Recherche et de Formation sur le Paludisme
Ouagadougou, Burkina Faso
Related Publications (2)
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.
PMID: 28289025DERIVEDGoncalves 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.
PMID: 26952094DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alfred Tiono, PhD, MD
Centre national de recherche et de formation sur le paludisme
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 2, 2013
First Posted
September 5, 2013
Study Start
September 1, 2013
Primary Completion
July 1, 2015
Study Completion
July 1, 2015
Last Updated
September 2, 2015
Record last verified: 2015-09