None listed
Conditions
Brief summary
This is an open-label study in Central Vietnam to monitor the first-line artemisinin based combination therapy, Pyramax® (pyronaridine-artesunate) plus primaquine for the treatment of uncomplicated P. falciparum malaria and to evaluate chloroquine plus primaquine for the treatment of P. vivax malaria. Drug exposure will be determined by measuring patient’s blood drug concentrations after treatment. The prevalence of drug resistant parasites will be determined in blood samples collected from the patients before drug treatment using in vitro (phenotypic) drug susceptibility testing and molecular (genotypic) assays with validated molecular markers of drug resistance. The P. falciparum and P. vivax parasite populations will be genetically characterized. The new point-of-care hemozoin detection device (Gazelle) will be used to measure hemozoin concentration decline in patient’s blood samples after starting treatment to determine its feasibility in predicting either drug sensitive or resistant strains of malaria infections.
Interventions
Participants with blood film positive Plasmodium falciparum malaria will be treated with the fixed dose combination of pyronaridine-artesunate (registered as Pyramax) to kill the blood asexual stages. Each tablet of pyronaridine-artesunate contains 60 mg artesunate + 180 mg pyronaridine. The dose of pyronaridine-artesunate will be in accordance to the participant's body weight with the target dosage range for pyronaridine–artesunate of 15.0 to 8.3 mg/kg/day of body weight for pyronaridine and 5.
Participants with blood film positive Plasmodium falciparum malaria will be treated with the fixed dose combination of pyronaridine-artesunate (registered as Pyramax) to kill the blood asexual stages. Each tablet of pyronaridine-artesunate contains 60 mg artesunate + 180 mg pyronaridine. The dose of pyronaridine-artesunate will be in accordance to the participant's body weight with the target dosage range for pyronaridine–artesunate of 15.0 to 8.3 mg/kg/day of body weight for pyronaridine and 5.0 to 2.5 mg/kg/day of body weight for artesunate. Pyronaridine–artesunate will be administered orally, at about 24 hour intervals for the 3 consecutive days. Also, on the first day of treatment patients will be coadministered a single oral dose of primaquine (0.5 mg/kg) to kill sexual stages of falciparum malaria to prevent transmission. Each tablet of primaquine contains 7.5 mg of primaquine base. Adherence to dosing with Pyramax and primaquine will be by direct observation. This regimen is the first-line treatment for falciparum malaria infections in Vietnam. Patients who are infected with P. vivax malaria and are Glucose-6-Phosphate Dehydrogenase (G6PD) normal will be treated with a standard oral course of chloroquine (25 mg/kg daily over 3 days) and primaquine (0.25 mg/kg) daily for 14 days. Each tablet of chloroquine contains 150 mg of chloroquine base and each tablet of primaquine contains 7.5 mg of primaquine base. Chloroquine has blood stage activity against vivax malaria whereas primaquine acts against the sexual and dormant liver stages of vivax malaria. Adherence to dosing with chloroquine and primaquine for the first 3-days will be by direct observation and the remaining 11 daily doses of primaquine will be unsupervised. Initially, for the treatment of vivax malaria we were planning to use a new regimen of chloroquine (25 mg/kg) over 3 days and a single oral dose of tafenoquine (300 mg). Tafenoquine is a similar drug to primaquine but has a much longer half-life in the blood (15 days versus 6 hours). However, because we have experienced a problem in sourcing tafenoquine from GlaxoSmithKline due to extenuating pandemic circumstances, we have decided to use the alternative intervention treatment of chloroquine (3 days ) plus primaquine (daily for 14 days). Chloroquine plus primaquine is registered as first-line treatment of vivax malaria in Vietnam and worldwide. Ethics approval from the Vietnam Ministry of Health has been obtained to replace chloroquine plus tafenoquine with chloroquine plus primaquine.
Sponsors
Australian Defence Force Malaria and Infectious Disease Institute
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
5 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
• People infected with uncomplicated mono-infections of P. falciparum and uncomplicated mono-infections of P. vivax; • Malaria parasite density of P. falciparum (= 500 to < 100,000 parasites/µL); • Malaria parasite density of P. vivax (= 250 parasites/µL); • Children (=5 years and =20 kg to <18 years old) and adults (=18 to <60 years old) infected with P. falciparum, children (=5 to <18 years old) and adults (=18 to <60 years old) infected with P. vivax malaria; • Gender: Males and females; • Working or residing at the study commune; • Able to provide information and capillary finger prick blood samples; • Written informed consent given to participate in the study by the adult or in case of children up to <18 years old (Assent form for children aged 12 to <18 years old) with parent or guardian permission; • Normal G6PD enzyme activity levels (>70%) of the site median value for G6PD normals for participants to be treated with primaquine for the radical cure of P. vivax malaria.
Exclusion criteria
• People not infected with malaria infections; • Children (<5 years old and <20 kg)infected with P. falciparum and less than 5 years of age infected with P. vivax malaria; • Unwilling to provide consent, information, and capillary finger prick blood sample; • Inability to communicate well with the study staff (poor mental development or evidence of psychiatric disorder); • People with P. vivax malaria who have G6PD deficient enzyme activity; • Pregnant or lactating females; • Any condition that in the judgment of the IMPE-QN/MIPM doctor would make participation in the study unsafe for the potential participant.
Outcome results
None listed