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The purpose of this study is to compare the gametocytocidal and transmission reducing activity of artemether-lumefantrine (AL) with and without a single dose of 0.25mg/kg primaquine (PQ) and sulfadoxine-pyrimethamine with amodiaquine (SPAQ) with and without single dose of 1.66mg/kg tafenoquine (TQ). Outcome measures will include infectivity to mosquitoes at 2, 5 and 7 days after treatment, gametocyte density throughout follow-up, and safety measures including haemoglobin density and the frequency of adverse events.
Full protocol available on request.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Artemether-lumefantrine (AL) | Active Comparator | Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days. |
|
| AL with 0.25mg/kg primaquine (PQ) | Experimental | Subjects will receive artemether-lumefantrine (AL) twice daily for 3 days and a single dose of 0.25mg/kg primaquine (PQ) on the first day of AL treatment. |
|
| Sulphadoxine-pyrimethamine with amodiaquine (SPAQ) | Active Comparator | Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days. |
|
| SPAQ with 1.66mg/kg tafenoquine (TQ) | Experimental | Subjects will receive sulphadoxine-pyrimethamine with amodiaquine (SPAQ) once daily for 3 days and a single dose of 1.66mg/kg tafenoquine (TQ) on the first day of SPAQ treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Artemether-lumefantrine | Drug | Tablets containing 20/80 mg artemether and 120/480 mg lumefantrine will be administered according to weight as per manufacturer guidelines. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in mosquito infection rate assessed through membrane feeding assays (day 2 and day 7) | Within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and AL-PQ arms, and day 7 post-treatment in the SPAQ and SPAQ-TQ. | 3 days (days 0, 2 and 7): 7 day span |
| Measure | Description | Time Frame |
|---|---|---|
| Change in mosquito infection rate assessed through membrane feeding assays (all timepoints) | Within person percent change (presented as percent reduction) in mosquito infection rate from baseline to all feeding time-points, with comparison within and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Measure | Description | Time Frame |
|---|---|---|
| Parasite genomic and transcriptomic variation assessed in RNA | Parasite genotype and transcriptional analysis at baseline and at post-treatment timepoints. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| The impact of plasma biomarkers on malaria transmission efficiency |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alassane Dicko | Malaria Research and Training Center, Bamako, Mali | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Malaria Research and Training Centre | Bamako | Mali |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38705163 | Derived | Mahamar A, Smit MJ, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Dicko OM, Diallo M, Maguiraga SO, Sankare Y, Keita S, Samake S, Dembele A, Lanke K, Ter Heine R, Bradley J, Dicko Y, Traore SF, Drakeley C, Dicko A, Bousema T, Stone W. Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali. Lancet Microbe. 2024 Jul;5(7):633-644. doi: 10.1016/S2666-5247(24)00023-5. Epub 2024 May 2. |
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Anonymised individual participant data may be shared on a digital repository or upon reasonable request.
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This is a single blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded, but no placebo will be used. The study pharmacist will be unblinded and responsible for randomisation and treatment administration.
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| Primaquine Phosphate | Drug | The single dose of 0.25mg/kg PQ will be administered in an aqueous solution, according to a standard operating procedure (SOP) provided by the manufacturer. |
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|
| Sulphadoxine-pyrimethamine with amodiaquine | Drug | Sulfadoxine/pyrimethamine tablets contain 500mg sulfadoxine and 25mg pyrimethamine. Amodiaquine tablets contain 150mg amodiaquine (as hydrochloride). Tablets will be administered according to weight as per manufacturer guidelines. |
|
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| Tafenoquine | Drug | 100mg tafenoquine tablets are prepared into a 1mg/mL solution in water. Solution will be given according to weight as indicated per treatment arm in 5kg bands. |
|
|
| Mosquito infection rate assessed through membrane feeding assays |
Mosquito infection rate at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms. |
| 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Human infectivity to locally reared mosquitoes assessed through membrane feeding assays | Infectivity to mosquitoes at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Mosquito infection density assessed through membrane feeding assays | Oocyst intensity (in all/all infected mosquitoes) at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Gametocyte infectivity | Infectiousness to mosquitoes for a given gametocyte density (measured as mosquito infection rate/gametocyte) at all feeding time-points, with comparison within treatment arms compared to baseline, and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Asexual/sexual stage parasite prevalence | Male and female gametocyte prevalence at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms. Asexual and total parasite prevalence at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Asexual/sexual stage parasite density | Male and female gametocyte density at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms. Asexual and total parasite density at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Sexual stage parasite sex ratio | Male and female gametocyte sex ratio (proportion male) at all time-points, determined by microscopy or molecular assays, with comparison within treatment arms compared to baseline, and between arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Sexual stage parasite circulation time | Gametocyte circulation time (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Sexual stage parasite area under the curve (AUC) | Gametocyte area under the curve (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms. | 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Haemoglobin density | Haemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms. | 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Change in haemoglobin density | Within person percent change (presented as percent reduction) in haemoglobin density (g/dL) from baseline to all time-points, with comparison within and between arms. | 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Methaemoglobin density | Methaemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms. | 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28) |
| Change in methaemoglobin density | Within person percent change (presented as percent reduction) in methaemoglobin density (g/dL) from baseline to all time-points, with comparison within and between arms. | 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Incidence of adverse events | The frequency and prevalence of adverse events (all AE's, treatment related AE's, and haematological AE's) observed up to and including day 2, 7, and 14 post-treatment, and at all timepoints. | 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
Plasma biomarkers (antibodies and parasite protein) at baseline and at post-treatment timepoints. |
| 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| Human genomic variation analysis and association with parasite measure | Human genotype analysis at baseline (G6PD, CYP2D6, and HBB type) | day 0 |
| ALT/AST/Creatine density | ALT/AST/Creatine density at all time-points with comparison within treatment arms compared to baseline, and between arms. | 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span |
| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| ID | Term |
|---|---|
| D008288 | Malaria |
| 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 |
| C001205 | fanasil, pyrimethamine drug combination |
| D000655 | Amodiaquine |
| C055852 | tafenoquine |
| 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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