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Low Dose Primaquine for Clearance of Gametocytes (LOPRIM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01935882
Recruitment Status : Completed
First Posted : September 5, 2013
Last Update Posted : September 2, 2015
Sponsor:
Collaborators:
Radboud University
Centre national de recherche et de formation sur le paludisme
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

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

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Study Type : Interventional  (Clinical Trial)
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 : September 2013
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

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



Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   2 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

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


Locations
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Burkina Faso
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
Centre national de recherche et de formation sur le paludisme
Investigators
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Principal Investigator: Alfred Tiono, PhD, MD Centre national de recherche et de formation sur le paludisme
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT01935882    
Other Study ID Numbers: LOPRIM-1
First Posted: September 5, 2013    Key Record Dates
Last Update Posted: September 2, 2015
Last Verified: September 2015
Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Lumefantrine
Artemether
Primaquine
Artemether, Lumefantrine Drug Combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents