Trial design, study site, conduct and ethics
gastrointestinal symptoms, parasitaemia, abdominal pain, nausea, vomiting
INFECTIOUS DISEASES, ALLERGY, ADVERSE EVENTS, DRUG WITHDRAWAL, EVENTS, SEVERE ANEMIA, BLOOD
The clinical trial design and methodology have been described previously [G6PDd patients were treated with supervised primaquine (blister-packed 7.5 & 15 mg tablets, Centurion Laboratories, Vadodara, India), at a target dose of 0.75mg base/kg per week (At enrolment, a medical history was taken, a physical examination was performed, and antimalarial treatment initiated. Patients were reviewed weekly for the first 8 weeks and then monthly for one year. At each visit, blood was taken and Giemsa stained for microscopic examination for peripheral parasitaemia, and Hb concentration (HemoCue AB, Ängelholm, Sweden). Blood films were declared negative if no parasites were detected after examining 200 high power fields (1,000× magnification) on the thick film.The primary efficacy outcome was the incidence rate of all recurrent vivax parasitaemia over 12 months of follow up, i.e. the total number of detected Haematological safety outcome measures included: the incidence risk of severe anemia (Hb <7g/dL) and/or blood transfusion, and an acute drop in Hb >5g/dL over the first 56 days of follow up, the median fall in Hb concentration from baseline to D3 and D7, the nadir Hb concentration (defined as minimum Hb concentration recorded over 56 days), the median time to nadir Hb, the maximal fractional change of Hb concentration (calculated from the difference in Hb at nadir from baseline), and the proportion of patients who achieved complete Hb recovery (D90 Hb > baseline Hb concentration).Adverse events (AE) were graded using the National Institute of Allergy and Infectious Diseases Table for grading the severity of Adult and Pediatric adverse events. Solicited gastrointestinal symptoms in routine questionnaires included nausea, vomiting and abdominal pain between D0 and D13. Any AE leading to study drug withdrawal, and serious AEs over 12 months were also recorded, irrespective of their relationship to study drugs.Ethics approvals were obtained from the relevant national and local committees and authorities, the Oxford University Tropical Ethics Committee and the Human Research Ethics Committee of the Northern Territory Department of Health, Australia (