DIRECT-SAFE: A Randomized Controlled Trial of DIRECT Endovascular Clot Retrieval versus Standard Bridging Therapy

Peter J Mitchell, Bernard Yan, Leonid Churilov, Richard J Dowling, Steven Bush, Thang Nguyen, Bruce C V Campbell, Geoffrey A Donnan, Zhongrong Miao, Stephen M Davis, DIRECT-SAFE Investigators, Peter J Mitchell, Bernard Yan, Leonid Churilov, Richard J Dowling, Steven Bush, Thang Nguyen, Bruce C V Campbell, Geoffrey A Donnan, Zhongrong Miao, Stephen M Davis, DIRECT-SAFE Investigators

Abstract

Background and purpose: The benefit regarding co-treatment with intravenous (IV) thrombolysis before mechanical thrombectomy in acute ischemic stroke with large vessel occlusion remains unclear. To test the hypothesis that clinical outcome of ischemic stroke patients with intracranial internal carotid artery, middle cerebral artery or basilar artery occlusion treated with direct endovascular thrombectomy within 4.5 hours will be non-inferior compared with that of standard bridging IV thrombolysis followed by endovascular thrombectomy.

Methods: To randomize 780 patients 1:1 to direct thrombectomy or bridging IV thrombolysis with thrombectomy. An international-multicenter prospective randomized open label blinded endpoint trial (PROBE) (ClincalTrials.gov identifier: NCT03494920).

Results: Primary endpoint is functional independence defined as modified Rankin Scale (mRS) 0-2 or return to baseline at 90 days. Secondary end points include ordinal mRS analysis, good angiographic reperfusion (modified Thrombolysis in Cerebral Infarction score [mTICI] 2b-3), safety endpoints include symptomatic intracerebral hemorrhage and death.

Conclusion: s DIRECT-SAFE will provide unique information regarding the impact of direct thrombectomy in patients with large vessel occlusion, including patients with basilar artery occlusion, with comparison across different ethnic groups.

Keywords: Ischemic stroke; Thrombectomy; Thrombolytic therapy.

Figures

Figure 1.
Figure 1.
Study assessment flow chart. NIHSS, National Institutes of Health Stroke Scale; CT, computed tomography; CTA, computed tomography angiography; MRA, magnetic resonance angiography; IV, intravenous; R, randomization; MT, mechanical thrombectomy; IVT, intravenous thrombolysis; MRI, magnetic resonance imaging; mRS, modified Rankin Scale.

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