GOLIATH 2018.

Study characteristics
Methods	Setting: single‐centre, Denmark RCT, 2 arms, open‐label, blinded endpoint Start date: 12 March 2015 (reported in protocol) Completion date: 2 February 2017 (reported in protocol)
Participants	128 men and women randomised: experimental GA group = 65, comparator CSA group (LA + CSA) = 63; lost to follow‐up (not reported); 128 analysed Mean age: 71.4 (SD 11.4) years Gender (men/women): 66/62 Mean NIHSS score: 18 (IQR 14–21) 4/63 participants allocated to CSA (6.3%) who crossed over from the CSA to the GA arm but remained in the CSA group for ITT analysis IV r‐tPA before EVT: GA = 50 and CSA = 46 96 (75%) participants received IV r‐tPA before EVT  Diagnostic criteria: AIS with large vessels occlusions in the anterior circulation Inclusion criteria Aged ≥ 18 years Groin puncture performed within 6 hours from symptom onset or when last seen well NIHSS > 10 (reported only in protocol) mRS ≤ 2 (reported only in protocol) Occlusion of internal carotid artery, internal carotid artery terminus, M1, M2 (reported only in protocol)  Exclusion criteria Intubated at presentation or with a GCS score < 9, mRS score > 2 Because primary trial endpoint was infarct growth, study required a DWI‐MRI scan to establish a baseline (pre‐EVT) infarct volume Contraindication to MRI infarct > 70 mL Posterior circulation stroke (reported only in protocol) Allergy to anaesthetics (reported only in protocol)
Interventions	Experimental: GA Rapid sequence intubation with suxamethonium bolus 0.5–1 mg/kg, alfentanil bolus 0.02–0.03 mg/kg, and propofol bolus 1–5 mg/kg followed by 2–10 mg/kg/hour. Endotracheal intubation was followed by mechanical ventilation with attempted normoventilation. Anaesthesia was maintained with propofol (2–10 mg/kg/hour) and remifentanil (0.2–1.0 µg/kg/minute). Final dosage and combination of anaesthetic drugs were at the discretion of the attending neuroanaesthesiologist. If possible, participants were extubated in the neurointerventional suite immediately after the procedure Comparator: CSA In the neurointerventional suite, participants received a fentanyl bolus 25–50 µg, which was repeated as necessary. A propofol infusion of 1–2 mg/kg/hour was initiated, and adjusted as required. Decreases in blood pressure were treated with vasopressors (ephedrine/phenylephrine) to maintain blood pressure within recommended limits (SBP > 140 mmHg, MAP > 70 mmHg). Final dosage and combination of anaesthetic drugs were at the discretion of the attending neuroanaesthesiologist. Excluded medications: not reported
Outcomes	Primary outcome (specified) Growth of DWI lesion (time frame: 48–72 hours) Primary outcome (collected) Infarct growth, measured in millilitres Secondary outcomes (specified) Time from arrival to groin puncture and recanalisation (time frame: 1–2 hours) Blood pressure during intervention (time frame: 1–2 hours) mRS (time frame: 90 days) Secondary outcomes measures (collected) mRS scores after 90 days Time from arrival to groin puncture and recanalisation blood pressure levels during the intervention Safety outcomes (symptomatic haemorrhage, 90 day‐mortality, vessel injury, and clot migration to a previous unaffected territory) (not reported in protocol) Successful reperfusion (mTICI 2b–3) (not reported in protocol)
Notes	Conflicts of interest: quote: "The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article". Funding: quote: "The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Albert J Yoo received a research grant from Penumbra Inc. and Neuravi Inc.". Protocol: NCT02317237
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Block randomisation (with sizes 4, 6, and 8) was performed after stratification".
Allocation concealment (selection bias)	Unclear risk	Details were not fully described Quote: "Allocation of block size was also random".
Blinding of participants and personnel (performance bias)	High risk	Not described, but due to the nature of the interventions, we assumed that blinding of personnel was not possible.
Blinding of outcome assessment (detection bias)	Unclear risk	Quote: "The allocation to either GA or CS could not be blinded but was unknown by the imaging core laboratory that evaluated the primary outcome and by the nurse who evaluated the 90‐day mRS score".
Incomplete outcome data (attrition bias)	Low risk	There were 0 losses and crossover in 2 (6.3%) participants from CSA to the GA arm but remained in the CSA group for ITT analysis.
Selective reporting (reporting bias)	Low risk	All prespecified outcomes and 2 additional outcomes were reported in the final article.
Other bias	Low risk	No evidence of other bias related to this study.