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| Name | Class |
|---|---|
| Radboud University Medical Center | OTHER |
| Centre national de recherche et de formation sur le paludisme | OTHER_GOV |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Artemether-Lumefantrine | Active Comparator | Artemether-Lumefantrine combination |
|
| Artemether-Lumefantrine-Primaquine 0.25 | Experimental | Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine |
|
| Artemether-Lumefantrine-Primaquine 0.4 | Experimental | Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Artemether-lumefantrine combination | Drug |
| ||
| Artemether-Lumefantrine with a single dose of 0.25mg/kg primaquine |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Transmission to Anopheles gambiae mosquitoes | Mosquito membrane feeding assays will be used to determine the proportion of infected mosquitoes and the oocyst burden in infected mosquitoes. | day -1, day 3, day 7 |
| Haematological recovery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alfred Tiono, PhD, MD | Centre national de recherche et de formation sur le paludisme | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre National de Recherche et de Formation sur le Paludisme | Ouagadougou | Burkina Faso |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28289025 | Derived | 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. | |
| 26952094 | Derived |
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| Drug |
|
| Artemether-Lumefantrine with a single dose of 0.4mg/kg primaquine | Drug |
|
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.
| 14 days during follow-up |
| Primaquine and lumefantrine pharmacokinetics | 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. | 7 days during follow-up |
| 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. |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
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| ID | Term |
|---|---|
| D000077611 | Artemether, Lumefantrine Drug Combination |
| D011319 | Primaquine |
| ID | Term |
|---|---|
| D000077549 | Artemether |
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
| D009930 | Organic Chemicals |
| D000078102 | Lumefantrine |
| D005449 | Fluorenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D011083 | Polycyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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