Hien 1996 VNM

Methods	Trial design: Double blind RCT Trial dates: Not stated
Participants	Number of participants: 560 adults aged 15 to 79 years enrolled Inclusion criteria: Patients were included in the trial if they (or an accompanying relative) gave informed consent, had asexual forms of P. falciparum on a peripheral‐blood smear, were older than 14 years, were not in the first trimester of pregnancy, were not intravenous drug users, had received less than 3 g of quinine or two doses of artemisinin or a derivative in the previous 48 hours, and had one or more of the following: a score on the Glasgow Coma Scale of less than 11 (indicating cerebral malaria); anaemia (hematocrit, 20 percent), with a parasite count exceeding 100,000 parasites/mm3 on a peripheral‐blood smear; jaundice (serum bilirubin, 2.5 mg/dL (50 mmol per litre)), with a parasite count of more than 100,000 parasites/mm3 on a peripheral‐blood smear; renal impairment (urine output, 400 mL per 24 hours; and serum creatinine, 3 mg/dL (250 mmol/L)); hypoglycaemia (blood glucose, 40 mg/dL (2.2 mmol/L)); hyperparasitaemia (10% parasitaemia); and systolic blood pressure below 80 mmHg with cool extremities (indicating shock). Exclusion criteria: None stated
Interventions	1.Intramuscular artemether (Kunming Pharmaceutical) Loading dose of 4 mg/kg Followed by 2 mg/kg eight hourly for a minimum of three days Followed by either a single oral dose of 15 mg of mefloquine or oral dose of 10 mg quinine sulphate for up to four days 2.Intramuscular quinine Loading dose of 20 mg/kg Followed by 10 mg/kg per kilogram eight hourly Followed by either a single oral dose of 15 mg/kg of mefloquine or oral dose of 10 mg/kg quinine sulphate for up to four days
Outcomes	Outcomes included in the review: Death Coma resolution time Neurological sequelae Fever clearance time Parasite clearance time Hypoglycaemia Need for blood transfusion Adverse effects Outcomes not included in the review: Duration of parenteral antimalarial treatment Time for plasma lactate level to fall below 2.5 mmol/L
Notes	Location: Special Research Ward, Centre for Tropical Diseases, Ho Chi Minh City, Vietnam Transmission: Not stated Funding: Wellcome Trust
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Trial authors provided no information on methods of sequence generation.
Allocation concealment (selection bias)	Low risk	"The drugs for each patient were placed in a coded sealed envelope 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	"To maintain blinding, a separate team of nurses, who were not otherwise involved with the care of the study patients, drew up and gave the injections. The drugs were kept in an opaque packet in a locked cabinet during the study". Both interventions were administered by intramuscular injection so blinding was feasible."
Blinding (performance bias and detection bias) Subjective outcomes: Others	Low risk	"To maintain blinding, a separate team of nurses, who were not otherwise involved with the care of the study patients, drew up and gave the injections. The drugs were kept in an opaque packet in a locked cabinet during the study". Both interventions were administered by intramuscular injection so blinding was feasible."
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up were recorded.
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting.
Other bias	Low risk	No other bias identified.