Phu 2010.

Methods	Trial design: double‐blind RCT Trial dates: May 1996 to June 2003
Participants	Number of participants: 370 adults aged between 15 and 77 years enrolled Inclusion criteria: peripheral blood smears had asexual forms of P falciparum and had at least 1 of the following severe complications: cerebral malaria (Glasgow Coma Score was less than 11); renal acute failure (oliguria and serum creatinine > 250 μmol/L); jaundice (total serum bilirubin > 50 μmol/L) with a parasite count of more than 100,000/μL or with serum creatinine > 250 μmol/L; hypoglycaemia (blood glucose < 2.2 mmol/L); anaemia (haematocrit < 20%) with a parasite count of more than 100,000/μL; hyperparasitaemia (parasite count > 500,000/μL); hyperlactataemia (plasma lactate > 4 mmol/L); metabolic acidosis (standard base excess ≥ 5 mmol/L, base deficit < 10 mmol/L); shock (systolic blood pressure < 80 mmHg with cool extremities). Exclusion criteria: patients were not included if they were < 14 years, were pregnant in the first trimester, were known intravenous drug abusers, had received more than 3 g of quinine or 2 doses of any artemisinin derivatives in the previous 48 hours before admission, had a past history of allergy to any artemisinin derivatives, or if known to be HIV positive.
Interventions	Intramuscular artemether (Kunming Pharmaceutical Company, Kunming, China) Loading dose of 3.2 mg/kg... ...followed by 1.6 mg/kg daily for at least 2 days. Intramuscular artesunate (Guilin No 2 Pharmaceutical Factory, Guangxi, China) Loading dose of 2.4 mg/kg on admission... ...followed by 1.2 mg/kg once daily for at least 2 days... ...followed by 2 mg/kg of oral artesunate to complete a total of 7 days.
Outcomes	Outcomes included in the review: Death Coma resolution time Time to discharge Fever clearance time Parasite clearance time Episodes of hypoglycaemia Adverse effects Outcomes not included in the review: Time to drinking Time to eating Time to sitting Time to standing Time to walking
Notes	Location: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam Transmission: not stated Funding: Wellcome Trust, UK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomization was generated from random number tables".
Allocation concealment (selection bias)	Low risk	"Labels with the name of drug for each patient were put in coded sealed opaque envelopes, and the envelopes were randomized in blocks of 20. Once a patient was enrolled in the study the envelope was opened".
Blinding (performance bias and detection bias) Objective outcome: Death	Low risk	"An independent team of nurses, not otherwise involved in the study or responsible for the care of these patients, open the envelope, randomized the patient and prepared the injection. Neither the treating physicians, study doctors and nurses, or patients knew which anti‐malarial drugs was administered".
Blinding (performance bias and detection bias) Subjective outcomes: Others	Low risk	"An independent team of nurses, not otherwise involved in the study or responsible for the care of these patients, open the envelope, randomized the patient and prepared the injection. Neither the treating physicians, study doctors and nurses, or patients knew which anti‐malarial drugs was administered".
Incomplete outcome data (attrition bias) All outcomes	Low risk	No loss to follow‐up recorded.
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting.
Other bias	Low risk	No other bias identified.