Results
–5·6, diarrhoea, blood stage, myalgia, anaemia, gastrointestinal intolerance, abdominal pain, gastritis, vomiting, peripheral parasitaemia, Fever, sepsis
ANAEMIA, ACUTE GASTRITIS, ADVERSE EVENTS, GASTRITIS, EVENT, LOSS OF APPETITE, ADVERSE EVENT, EVENTS, SEPSIS
Between Aug 18, 2019, and March 14, 2022, a total of 1563 patients were screened for inclusion. Due to the COVID-19 pandemic the study was interrupted after enrolment was completed in Bangladesh but before enrolment could start in Ethiopia and Indonesia (CONSORT diagramG6PD=glucose-6-dehydrogenase. *Of the five patients randomly assigned but not included in the analysis, three were assigned to the high-dose primaquine arm and two to the standard care arm.Baseline characteristicsData are n (%), median (IQR), or mean (SD), unless otherwise specified. G6PD=glucose-6-dehydrogenase. Schizontocidal treatment of blood stage parasites plus 7 mg/kg total dose of primaquine given over 7 days.Schizontocidal treatment of blood stage parasites plus a single dose of primaquine to elimate the sexual parasite stages.Defined as axillary temperature of ≥37·5°C.At day 63, the incidence risk of any Risk of Kaplan-Meier graph showing the risk of any Efficacy outcomesData are median (IQR). HR=hazard ratio.Schizontocidal treatment of blood stage parasites plus 7 mg/kg total dose of primaquine given over 7 days.Schizontocidal treatment of blood stage parasites plus a single dose of primaquine to elimate the sexual parasite stages.95% CI estimated as a proportion of N at risk on day 7 using the binomial exact method.Could not be estimated due to zero events in the intervention arm.Risk of Artemether–lumefantrine was used in Bangladesh and Ethiopia and dihydroartemisinin–piperaquine was used in Indonesia. For subgroups where no outcome events were observed, the 95% CI was estimated as a proportion of N at risk on day 7 using the binomial exact method.The incidence risk of symptomatic At enrolment, Fever clearance was similar between groups with 98 (91%) of 108 patients becoming afebrile within 24 h of starting treatment in the standard care arm compared with 96 (84%) of 114 in the intervention arm (p=0·14). Overall, 454 (93%) of 487 patients with peripheral parasitaemia had complete parasite clearance within 2 days of starting treatment, with no significant difference between treatment groups (p=0·96; A routine symptom checklist was done on day 2 and day 7 in both treatment arms. Gastrointestinal tolerability was similar between arms. In the standard care arm 16 (7%) of 237 patients reported vomiting, seven (3%) of 236 reported diarrhoea, and 92 (39%) of 237 reported loss of appetite on day 2. The corresponding proportions in the intervention arm were 6% (15 of 235), 2% (4 of 235), and 37% (88 of 235). On day 7 gastrointestinal intolerance was low and similar between both treatment arms (Safety and tolerability outcomesSchizontocidal treatment of blood stage parasites plus 7 mg/kg total dose of primaquine given over 7 days.Schizontocidal treatment of blood stage parasites plus a single dose of primaquine to elimate the sexual parasite stages.Related events include those that are possibly, probably, or definitely related.Reported retrospectively on day 7 for patients in the standard care arm.Denominators are total number of doses.Denominators vary based on availability of data.A total of 143 adverse events were reported between enrolment and day 42, of which 132 (92%) were mild (grade 1; 71 (50%) of the 143 adverse events were reported before or on day 7 (54 in the intervention arm and 17 in the standard care arm). Patients in the intervention arm had scheduled visits on days 3–6 in which adverse events were assessed; 29 (54%) of the reported events for this group occurred on those visit days. Patients in the standard care arm did not have scheduled visits on days 3–6 and reported events retrospectively at their day 7 visit; two (12%) of the 17 events reported for this group occurred during days 3–6 (One adverse event was reported as grade 3 occurring in a patient enrolled in the intervention arm. The patient was an 18-year-old male presenting with acute gastritis and vomiting on day 5, treated as an outpatient with an antiemetic. He continued his primaquine course and recovered within 5 days.There were two serious adverse events reported, both of which occurred in the intervention arm. The first event was in a male patient aged 24 years who was admitted to hospital with severe abdominal pain on day 7, after completing primaquine treatment. He had been taking non-steroidal, anti-inflammatory drugs for several years for myalgia after physical activity. The event was considered to be possibly related to the study drug compounded by underlying gastritis. The patient made a rapid recovery and was discharged the following day. The second event was in a male patient aged 45 years who presented with abdominal pain on day 25 and signs of sepsis, both of which were considered to be unrelated to the study drug. He was treated with ciprofloxacin, analgesia, and intravenous fluids in hospital. He made a rapid recovery and was discharged the following day.The mean haemoglobin concentration at enrolment was 14·1 g/dL (SD 2·5, range 8·1 to 24·2) and was similar between treatment arms. The mean haemoglobin fell to 12·6 g/dL in the intervention arm and to 12·7 g/dL in the standard care arm on day 2 and was 13·5 g/dL in the intervention arm and 13·9 g/dL in the standard care arm on day 7. On day 2 the unadjusted mean absolute change in haemoglobin relative to baseline was –0·5 g/dL (range –4·6 to –4·4) in the standard care arm and –0·3 g/dL (–9·2 to 5·7) in the intervention arm. By day 7, the unadjusted mean absolute change in haemoglobin relative to baseline was –0·1 g/dL (–5·6 to 6·4) in the standard care arm and –0·7 g/dL (–6·9 to 8·7) in the intervention arm (None of the patients developed severe anaemia (haemoglobin of <5 g/dL; 