Poravuth 2011.

Methods	RCT Duration: 1 year, March 2007 to March 2008
Participants	Adults and children with P vivax malaria Number: 456 Inclusion criteria: age 3 ‐ 60 years; fever or history of fever within 24 hours; bodyweight 20 kg ‐ 90 kg Exclusion criteria: severe/complicated malaria; mixed Plasmodium infection; severe vomiting; other clinical condition recurring hospitalization; other clinically significant disorder; viral hepatitis/HIV; malnutrition; QTc ≥ 450 ms; other febrile conditions; hepatic impairment (AST/ALT > 2.5 x ULN); renal impairment; anaemia (Hb < 8 g/dL); allergy to study drugs; antimalarial therapy in previous 2 weeks (or antibacterial with antimalarial effect); investigational drug in previous 4 weeks; previous participation in pyronaridine‐artesunate studies; pregnancy/lactation; unable to comply with follow‐up visits Diagnosis: microscopy of P vivax (parasite density ≥ 250/mL blood, including > 50% asexual parasites)
Interventions	Pyronaridine‐artesunate tablets (180 mg:60 mg) once‐daily for 3 days. Dose according to bodyweight: 20 kg ‐ 25 kg one tablet; 26 kg ‐ 44 kg two tablets; 65 kg ‐ 90 kg, 3 tablets. Range = 7.2/2.4 to 13.8/4.6 mg/kg/dose Chloroquine 620 mg on day 0 and 1, and 310 mg on day 2. The chloroquine target dose for children was 10 mg/kg on days 0 and 1, and 5 mg/kg on day 2
Outcomes	Adverse events Cure rate day 14* Cure rates day 21, 35, and 42* Fever clearance time (from first dose to apyrexia)†* Proportions afebrile and aparasitaemic on days 1, 2, and 3* *Not assessed in quantitative synthesis in this review †Two consecutive normal readings taken between 7 and 25 hours apart
Notes	Location: Asia (Cambodia, India, Indonesia, and Thailand) Setting: local hospitals Malaria endemicity: high Resistance profile: not described Source of funding: Medicines for Malaria Venture, Shin Poong Pharmaceutical Company Ltd, Seoul, Republic of Korea Follow‐up: 42 days
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generated randomization scheme
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes
Blinding (performance bias and detection bias) All outcomes	Low risk	Doubly‐dummy ‐ study drug and matching placebo, packaged similarly All study investigators, laboratory technicians, and patients blind to treatment assignment Investigator calculated the appropriate dose and study drug was administered by a different member of staff
Incomplete outcome data (attrition bias) All outcomes	Low risk	Report lists reasons for attrition and exclusions
Selective reporting (reporting bias)	Low risk	Prospectively registered. Report includes all prestated outcomes of interest
Other bias	Low risk	3 authors declared conflicting interests (employees of funders); blind to treatment allocation
Adverse event monitoring (detection bias) Adverse Events	Unclear risk	Authors do not fully describe method for detection of adverse events, but describe interval for ECG assessment. Authors do not give definitions of all adverse events
Incomplete adverse event reporting (reporting bias) Adverse events	Low risk	All‐cause adverse events enumerated. Report table only includes adverse events occurring in ≥ 2% (or ≥ 1% if judged to be drug‐related)