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 y.o. •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 y.o. •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 4h15min from onset)	•Age 18–85 y.o. •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 h from onset)	•Age ≥18 y.o. •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 y.o. •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 4h15min from onset)	•Age ≥18 y.o. •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 6hrs 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
Centres	41 academic tertiary care centres in China	33 tertiary stroke centres in China	23 MT-capable stroke centres in Japan	20 MT-capable stroke centres in the Netherlands, Belgium and France	48 centres in Switzerland, Germany, UK, France, Austria, Finland, Spain, and Canada	25 centres 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 programme grant and Stryker<!

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