Malaria
Conditions
Brief summary
The purpose of this study is to determine the most efficacious transmission blocking drug regimen for seasonal malaria chemoprophylaxis in Mali. The primary outcome measure will be the proportion of mosquitoes infected pre and post-treatment, assessed through membrane feeding and measured by oocyst prevalence in mosquitoes dissected on day 7 post feed. Primary endpoint will be a within group comparison between the mean of the pretreatment infectivity (Day 0) and infectivity at 7 days post first dose.
Detailed description
Protocol will be shared on request.
Interventions
Each Fansidar tablet is scored containing 500mg sulphadoxine and 25 mg pyrimethamine. Doses will be administered by weight.
Primaquine will be administered in an aqueous solution according to weight-based dosing.
DRUGDihydroartemisinin-piperaquine
160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets will be used to administer weight-based doses.
DRUGMethylene blue
Methylene blue will be given as minitablets in prepackaged sachets according to weight groups.
DRUGAmodiaquine
Amodiaquine will be administered once daily for 3 days, following weight-based dosing of 150 mg tablets.
Sponsors
Malaria Research and Training Center, Bamako, Mali
Radboud University Medical Center
London School of Hygiene and Tropical Medicine
Heidelberg University
Bill and Melinda Gates Foundation
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
5 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Glucose-6-phosphate dehydrogenase (G6PD) normal defined by CareStart™ G6PD rapid diagnostic test (RDT) or the OSMMR2000 G6PD semi-qualitative test * Absence of symptomatic falciparum malaria, defined by fever upon enrollment * Presence of P. falciparum gametocytes on thick blood film at a density \>30 gametocytes/µL (i.e. ≥2 gametocytes recorded in the thick film against 500 white blood cells) * No allergies to study drugs * No self-reported use of antimalarial drugs over the past 7 days (as reported by the participant) * Hemoglobin ≥ 10 g/dL * Individuals weighing \<80 kg * No evidence of severe or chronic disease * Written, informed consent
Exclusion criteria
* Age \< 5 years or \> 50 years * Female gender * Blood thick film negative for sexual stages of malaria * 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 * Use of other medications (with the exception of paracetamol and/or aspirin) * Consent not given
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mosquito infectivity assessed through membrane feeding assays | 7 day | Infectivity will be measured by oocyst prevalence in dissected mosquitoes. Primary endpoint will be a comparison between mean of pretreatment infectivity (day 0) and infectivity at days 2 and 7 post first dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination half life (t1/2) of primaquine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Peak plasma concentration (Cmax) of methylene blue | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Gametocyte prevalence, density, and sex ratio measured microscopically and by molecular methods. | 42 days | Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose. |
| Asexual parasite prevalence and density | 42 days | Asexual parasitemia will be evaluated by blood smear microscopy and confirmed by more sensitive, molecular methods. Outcome measured at baseline and days 1, 2, 3, 7, 14, 28, and 42 post first dose. |
| Safety measurements including hemoglobin and signs of hemolysis | 42 days | The major safety endpoint is hemolysis. For this reason, hemoglobin and methemoglobin values will be measured before treatment, at baseline and on days 1, 2, 3, 7, 14, 28, and 42 post first dose. In addition, clinical review (including additional signs of hemolysis) will be assessed based on active and passive follow-up. |
| Peak plasma concentration (Cmax) of primaquine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Area under the concentration curve (AUC) of methylene blue | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Area under the concentration curve (AUC) of primaquine. | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Peak plasma concentration (Cmax) of sulphadoxine-pyrimethamine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Area under the concentration curve (AUC) of sulphadoxine-pyrimethamine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Elimination half-life (t1/2) of sulphadoxine-pyrimethamine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Peak plasma concentration (Cmax) of dihydroartemisinin-piperaquine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Area under the concentration curve (AUC) of dihydroartemisinin-piperaquine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Elimination half-life (t1/2) of dihydroartemisinin-piperaquine | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
| Identification of cytochrome P450 (CYP) 2D6 and G6PD polymorphisms | 1 hour | CYP2D6 and G6PD genotyping will be performed using Thermo Fisher Scientific OpenArray Technology and Copy Number Variation (CNV) assays on the QuantStudio™ 12K Flex Real-Time PCR System. |
| Elimination half life (t1/2) of methylene blue | 24 hours | Outcome measured at hours 1, 2, 4, 6, 8, and 24 post first dose. |
Countries
Mali
Outcome results
None listed