Dondorp 2005.

Methods	Study design: An open label multi‐centre randomized controlled trial Study dates: Jun 2003 to May 2005
Participants	Number: 1461 enrolled Inclusion criteria: adults and children > 2 yr with severe malaria (positive blood antigen stick test for P. falciparum and a diagnosis of severe malaria, according to the admitting physician) Exclusion criteria: convincing history of full treatment with quinine (40 mg/kg on the first day and 30 mg/kg on any subsequent day) or an artemisinin derivative for more than 24 h before admission, known allergy to 1 of the artemisinin derivatives or quinine
Interventions	1. Artesunate: 2.4 mg/kg intravenous (IV) at 0, 12, and 24 h then 2.4 mg/kg IV every 24 h until able to swallow then 2 mg/kg by mouth until day 7 2. Quinine: 20 mg/kg IV loading dose then 10 mg/kg every 8 h until able to swallow then 10 mg/kg by mouth every 8 h until day 7 Additional antimalarials: both arms except in India and Bangladesh were given doxycycline (100 mg every 12 h for 7 d) once able to swallow
Outcomes	1. In‐hospital death 2. Death within 48 h of entry 3. Death after 48 h of entry 4. In‐hospital death (blood‐smear positive) 5. Neurological sequelae 6. Time to discharge (median, intra quartile range, and range) 7. Hypoglycaemia after entry Not included in the review: 8. Combined outcome: in hospital death or neurological sequelae 9. Fetal death 10. Time to speak (median, intra quartile range, and range) 11. Time to eat (median, intra quartile range, and range) 12. Time to sit (median, intra quartile range, and range) 13. Convulsions after entry 14. Shock developing after entry 15. Blackwater fever developing after entry 16. Dialysis after entry 17. Vasopressor treatment after entry 18. Mechanical ventilation after entry
Notes	Location: hospitals in Bangladesh, Myanmar, India, and Indonesia Transmission: not specified Funding: Wellcome Trust grant
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: 'The two‐step randomisation was produced with a computer generated randomisation list'
Allocation concealment (selection bias)	Low risk	Quote: 'After informed consent was obtained, we signed and dated a numbered sealed envelope across the seal, then opened it to reveal a unique study number. This number did not indicate the treatment allocation, but referred to a separate sealed hardcover box, containing the study drug, case record form, and all disposables needed for drug administration and blood sampling'
Blinding (performance bias and detection bias) Objective outcomes: Death	Low risk	Comment: An open‐label trial is unlikely to bias an objective outcome like death
Blinding (performance bias and detection bias) Subjective outcomes: Others	High risk	Comment: An open label trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up are recorded.
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting
Other bias	Low risk	No other bias identified