Randomization of endovascular treatment with stent-retriever and/or thromboaspiration versus best medical therapy in acute ischemic stroke due to large vessel occlusion trial: Rationale and design

Background RESILIENT is a prospective, multicenter, randomized phase III trial to test the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. Methods Subjects must fulfill the following main inclusion criteria: symptom onset <= 8 h, age >= 18 years, baseline NIHSS >= 8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS >= 6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. Randomization Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. Design The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0-2 at 90 days) common odds ratio of 1.615. Primary outcome Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. Secondary outcomes Secondary end-points include: 90-day functional independence (mRS <= 2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0-2 or improvement >= 8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.