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ID
Source
Brief title
Health condition
Malaria
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. 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.
[Time Frame: 3 days (days 0, 2 and 7): 7 day span]
Secondary outcome
2. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
3. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
4. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
5.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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
6. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
7. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
8. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
9. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
10. Sexual stage parasite circulation time
Gametocyte circulation time (cumulative), determined by microscopy or molecular assays, compared within and between treatment arms.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
11. 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.
[Time Frame: 7 days (day 0, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
12. Haemoglobin density
Haemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms.
[Time Frame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
13. 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.
[Time Frame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
14. Methaemoglobin density
Methaemoglobin density (g/dL) at all time-points, with comparison within treatment arms compared to baseline, and between arms.
[Time Frame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28)]
15. 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.
[Time Frame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
16. 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.
[Time Frame: 8 days (day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28): 28 day span]
Background summary
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.
Study objective
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).
Study design
day 0, day 1, day 2, day 5, day 7, day 14, day 21, day 28
Intervention
Artemether-lumefantrine (20/80 mg artemether and 120/480 mg lumefantrine), Primaquine Phosphate (0.25mg/kg), Sulphadoxine-pyrimethamine with amodiaquine (500mg sulfadoxine and 25mg pyrimethamine and 150mg amodiaquine), Tafenoquine (1.66mg/kg)
Inclusion criteria
- Age ≥ 10 years and ≤ 50 years
- G6PD-normal defined by Carestart rapid diagnostic test or the OSMMR2000 G6PD qualitative test
- Absence of symptomatic falciparum malaria, defined by fever on enrolment
- Presence of P. falciparum gametocytes on thick blood film at a density >16 gametocytes/μL (i.e. ≥ gametocytes recorded in the thick film against 500 white blood cells)
- Absence of other non-P. falciparum species on blood film
- Hemoglobin ≥ 10 g/dL
- Individuals weighing < = 80 kg
- No evidence of acute severe or chronic disease
- Written, informed consent
Exclusion criteria
- Women who are pregnant or lactating (tested at baseline). Urine and/or serum pregnancy testing (β-hCG) will be used.
- Detection of a non-P. falciparum species by microscopy
- Previous reaction to study drugs / known allergy to study drugs
- Signs of severe malaria, including hyperparasitemia (defined as asexual parasitemia > 100,000 parasites / μL)
- Signs of acute or chronic illness, including hepatitis
- The use of other medication (except for paracetamol and/or aspirin)
- Use of antimalarial drugs over the past 7 days (as reported by the participant)
- Clinically significant illness (intercurrent illness e.g., pneumonia, pre-existing condition e.g., renal disease, malignancy or conditions that may affect absorption of study medication e.g., severe diarrhea or any signs of malnutrition as defined clinically)
- Signs of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e., decompensated cirrhosis, Child Pugh stage B or C)
- Signs, symptoms or known renal impairment
- Clinically significant abnormal laboratory values as determined by history, physical examination or routine blood chemistries and hematology values (laboratory guideline values for exclusion are hemoglobin < 10 g/dL, platelets < 50,000/μl, White Blood - Cell count (WBC) < 2000/μl, serum creatinine >2.0mg/dL, or ALT or AST more than 3 times the upper limit of normal for age.
- Blood transfusion in the last 90 days.
- Consistent with the long half-life of tafenoquine, effective contraception should be continued for 5 half-lives (3 months) after the end of treatment.
- History of psychiatric disorders
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| NTR-new | NL9777 |
| Other | LSHTM Research Ethics Committee : 26257 |