Rueangweerayut 2012.

Methods	RCT Duration: 1 year, 10 months. January 2007 to October 2008
Participants	Adults and children with P falciparum malaria Number: 1271 Inclusion criteria: age 3‐60 years; bodyweight 20 kg ‐ 90 kg; fever or history of fever within 24 hours Exclusion criteria: severe/complicated malaria; anaemia (Hb < 8 g/dL); severe vomiting; diarrhoea; pregnancy/lactation; other clinically significant disorder; hepatic impairment (undefined); renal impairment; antimalarial therapy in previous 2 weeks; investigational drug in previous 4 weeks; previous participation in study; allergy to study drugs Diagnosis: thick and thin film microscopy of P falciparum (asexual parasite density 1000 mm3‐ 100,000 mm3 blood)
Interventions	Randomized in a 2:1 ratio to: pyronaridine‐artesunate combination (7.2: 2.4 mg/kg respectively) once a day for three days (N = 848) mefloqune ‐artesunate combination (6.2 to 12.5 mg/kg and 2.2 to 5.0 mg/kg respectively) once a day for three days (N = 423)
Outcomes	ACPR* day 28 PCR‐adjusted ACPR day 28 unadjusted ACPR day 42 PCR‐adjusted ACPR day 42 unadjusted Parasite clearance time (from first dose to aparasitaemia)†, ‡ Fever clearance time (from first dose to apyrexia)†, ‡ Proportion of patients with parasite clearance on days 1, 2, and 3, ‡ Proportion of patients with fever clearance on days 1, 2, and 3, ‡ Proportion of patients with gametocytes, ‡ Gametocyte clearance time (not defined)‡ Adverse events *Adequate clinical and parasitological response rate †Two consecutive normal readings taken between 7 and 25 hours apart ‡Not assessed in quantitative synthesis in this review
Notes	Location: Asia (81%) and Africa (19%). Asia: Cambodia, India, Thailand, Vietnam. Africa: Bukina Faso, Ivory Coast, Tanzania Setting: local hospitals and health centres Malaria endemicity: high Resistance profile: in Cambodia, significantly extended parasite clearance times (for both treatment arms) were suggestive of in vivo resistance to artemisinin 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 schedule
Allocation concealment (selection bias)	Low risk	Individually numbered treatment packs Randomization communicated by investigator to a third party who administered the correct amount of tablets
Blinding (performance bias and detection bias) All outcomes	Low risk	Unclear if patients blinded Outcome assessors blinded to group assignment
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	Some authors employed by trial sponsors, but all authors assumed responsibility for reporting accuracy
Adverse event monitoring (detection bias) Adverse Events	Unclear risk	Authors do not describe methods for monitoring adverse events, but includes biochemical monitoring Authors do describe time point of assessments in protocol
Incomplete adverse event reporting (reporting bias) Adverse events	Unclear risk	Report percentage of adverse events. Supplementary data table provided. Reports "any cause" adverse events if they occurred in > 2% of patients. Reports "treatment related" adverse events if they occurred in > 1% of patients. Does not report method of judging relation of adverse events to treatment