van Hensbroek 1996 GMB

Methods	Trial design: Open label trial Trial dates: 1992 to 1994
Participants	Number: 576 children aged one to nine years enrolled Inclusion criteria: Unconscious children one to nine years of age with a Blantyre coma score of 2 or less, asexual forms of P. falciparum were identified on a thick blood film, and a parent or guardian gave informed consent. Exclusion criteria: Patients with diseases other than malaria at the time of admission and those who recovered consciousness immediately after correction of hypoglycaemia or within one hour if they were convulsing on admission. Patients treated with quinine before admission.
Interventions	1. Intramuscular artemether (Paluther, Rhone‐Poulenc) Loading dose of 3.2 mg/kg on admission Followed by daily doses of 1.6 mg/kg for three days 2. Intravenous quinine (Rotexmedica, Germany) Loading dose of 20 mg/kg Followed by 10 mg/kg every 12 hours Then oral quinine once patient was able to swallow for a total of five days An oral dose of approximately 1.25 mg/kg pyrimethamine and 25 mg/kg sulfadoxine was given to both arms to reduce recrudescence (in the 2nd and 3rd years of the trial).
Outcomes	Outcomes included in the review: Death Coma resolution time Neurological sequelae at discharge Neurological sequelae at 28 days Fever clearance time Parasite clearance time Adverse effects Outcomes not included in the review: Residal neurological sequelae (five months follow‐up) 28th day cure rate
Notes	Location: Royal Victoria Hospital and Sibanor Health Centre,Banjul Gambia Transmission:Unknown Funding: UNDP/World Bank/WHO special programme for research and training in tropical diseases (TDR) The Netherlands Foundation for the Advancement of Tropical Research The Ter Meulen Foundation The Medical Research Council
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Trial authors do not provide details of sequence generation
Allocation concealment (selection bias)	Low risk	"The treatment code for each child was stored in a sealed envelope that was opened after the admission procedure was completed and parental consent had been obtained".
Blinding (performance bias and detection bias) Objective outcome: Death	Low risk	An open‐label trial is unlikely to bias an objective outcome like death.
Blinding (performance bias and detection bias) Subjective outcomes: Others	Low risk	"Each blood film was examined by two independent observers who were unaware of the treatment code".
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.