Low Dose Primaquine for Clearance of Gametocytes (LOPRIM)
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|ClinicalTrials.gov Identifier: NCT01935882|
Recruitment Status : Completed
First Posted : September 5, 2013
Last Update Posted : September 2, 2015
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||360 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 :||September 2013|
|Actual Primary Completion Date :||July 2015|
|Actual Study Completion Date :||July 2015|
Active Comparator: Artemether-Lumefantrine
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
- Gametocyte carriage [ Time Frame: 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.
- Transmission to Anopheles gambiae mosquitoes [ Time Frame: 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.
- Haematological recovery [ Time Frame: 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.
- Primaquine and lumefantrine pharmacokinetics [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01935882
|Centre National de Recherche et de Formation sur le Paludisme|
|Ouagadougou, Burkina Faso|
|Principal Investigator:||Alfred Tiono, PhD, MD||Centre national de recherche et de formation sur le paludisme|