Table 1

Overview of the design of each included RCT

Trial	DIRECT-MT	DEVT	SKIP	Mr CLEAN-NO IV	SWIFT-DIRECT	DIRECT-SAFE
Design	Non-inferiority RCT (PROBE)	Non-inferiority RCT (PROBE)	Non-inferiority RCT (PROBE)	Superiority RCT (PROBE)	Non-inferiority RCT (PROBE)	Non-inferiority RCT (PROBE)
Primary endpoint	mRS (cOR)	mRS 0–2	mRS 0–2	mRS (cOR)	mRS 0–2	mRS 0–2
Pre-specified non-inferiority margin, in relation with the primary endpoint	Relative: lower boundary of the CI of the cOR ≥0.80	Absolute: 10%	Relative: lower boundary of the CI of the OR ≥0.74	Relative: lower boundary of the CI of the cOR ≥0.80	Absolute: 12%	Absolute: 10%
Main inclusion criteria	Age ≥18 years Pre-stroke mRS ≤2 ICA, Ml or proximal M2 occlusion NIHSS ≥2 ASPECTS: no limit Eligible for IVT within 4.5 hours after symptom onset	Age ≥18 years Pre-stroke mRS ≤1 ICA or Ml occlusion NIHSS: no lower limit ASPECTS: no limit Eligible for IVT within 4.5 hours after symptom onset (randomization within 4 hours 15 min from onset)	Age 18–85 years Pre-stroke mRS ≤2 ICA or Ml occlusion NIHSS ≥6 CT-ASPECTS ≥6 or DWI-ASPECTS ≥5 Eligible for IVT within 4.5 hours after symptom onset (randomization within 4 hours from onset)	Age ≥18 years Pre-stroke mRS ≤2 ICA-T, Ml or proximal M2 occlusion NIHSS ≥2 ASPECTS: no limit Eligible for IVT within 4.5 hours after symptom onset	Age ≥18 years Pre-stroke mRS ≤1 ICA or Ml occlusion NIHSS ≥5 and <30 ASPECTS ≥4 (CT or MRI) Eligible for IVT within 4.5 hours after symptom onset (randomization within 4 hours 15 min from onset)	Age ≥18 years Pre-stroke mRS ≤3 ICA, Ml, M2 or basilar artery occlusion No hypodensity >1/3 MCA territory on non-contrast CT Eligible for IVT within 4.5 hours after symptom onset Arterial puncture possible within 6 hours of symptom onset
Thrombolytic agent	Alteplase 0.9 mg/kg	Alteplase 0.9 mg/kg	Alteplase 0.6 mg/kg	Alteplase 0.9 mg/kg	Alteplase 0.9 mg/kg	Alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg
Centers	41 academic tertiary care centers in China	33 tertiary stroke centers in China	23 MT-capable stroke centers in Japan	20 MT-capable stroke centers in the Netherlands, Belgium and France	48 centers in Switzerland, Germany, UK, France, Austria, Finland, Spain, and Canada	25 centers in China, Australia, Vietnam and New Zealand
Funding	Stroke Prevention Project of the National Health Commission of the People’s Republic of China and by the Wu Jieping Medical Foundation.	National Natural Science Foundation of China, Chongqing Major Disease Prevention and Control Technology Research Project, Clinical Medical Research Talent Training Program of Army Medical University, Major Clinical Innovation Technology Project of the Second Affiliated Hospital of Army Medical University.	Japanese Society for Neuroendovascular Therapy.	Dutch Heart Foundation; the Brain Foundation Netherlands; the Ministry of Economic Affairs; and unrestricted funding by Stryker, Medtronic, and Cerenovus.	Investigator initiated trial, supported by Medtronic, additional intramural funds Berne University Hospital	Investigator initiated trial, supported by an Australian NHMRC program grant and Stryker

ASPECTS, Alberta Stroke Program Early CT Score; cOR, common OR; CT, computed tomography; dMT, direct mechanical thrombectomy (MT alone); DWI, diffusion weighted imaging; ICA, internal carotid artery; IVT, intravenous thrombolysis with alteplase; M1, first segment of the middle cerebral artery; M2, second segment of the middle cerebral artery; MCA, middle cerebral artery; MRI, magnetic resonance imaging; mRS, modified Rankin Scale; MT, mechanical thrombectomy; NA, not available; NIHSS, National Institutes of Health Stroke Scale; PROBE, prospective randomized open blinded endpoint trial; RCT, randomized clinical controlled trial.