Llanos‐Cuentas 2019.

Study characteristics
Methods	Multicentre, double‐blind, double‐dummy RCT Trial phase: III Trial design: parallel‐group trial assessing primary safety outcomes
Participants	Number randomized: 251 Inclusion criteria: males and females aged ≥ 16 years with clinical symptoms of malaria with P vivax monoinfection with an asexual parasite density > 100/µL and < 100,000/µL of blood Exclusion criteria: receiving antimalarial treatment within 30 days of screening severe malaria, any clinically significant concurrent illness severe vomiting or Hb < 7 g/dL pregnancy, breastfeeding or G6PD enzyme activity < 70% of the site median for males (< 40% for females) mixed malaria prolonged QT interval on ECG or elevation of ALT < 2 times upper normal limit
Interventions	All participants received the standard adult dose of CQ (1500 mg) over 3 days to eradicate the current infection plus: TQ 300 mg single dose + PQ matched placebo (n = 166) PQ 15 mg/day for 14 days (n = 85)
Outcomes	Outcomes included in this review: recurrence of microscopically confirmed P vivax malaria after completing treatment up to 6 months adverse events attributable to TQ (including a drop in Hb > 3 g/dL or 30% from baseline) Outcomes not included in this review: number of recurrences at 4 months
Notes	Location: Peru, Thailand, Colombia, Brazil, Vietnam Setting: local hospitals Endemicity: endemic for vivax malaria Resistance: unknown Funding: GlaxoSmithKline, Medicines for Malaria Venture This study was designated as an ongoing study in the previous version of our review (NCT02216123)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation not mentioned. Quote: "The methods were similar to those used in the phase 3 DETECTIVE trial (Lacerda 2019)."
Allocation concealment (selection bias)	Unclear risk	Quote: "The methods were similar to those used in the phase 3 DETECTIVE trial (Lacerda 2019)."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, double‐dummy study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind study
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition rate in all groups < 4% of number randomized.
Selective reporting (reporting bias)	Low risk	Outcomes of all randomized participants reported.
Other bias	Low risk	None identified.

ALT: alanine aminotransferase; CQ: chloroquine; ECG: electrocardiogram; Hb: haemoglobin; G6PD: glucose‐6‐phosphate dehydrogenase; n: number of participants; PQ: primaquine; RCT: randomized controlled trial; TQ: tafenoquine.