Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial

Abstract

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes.

Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke.

Design, setting, and participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020).

Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group.

Main outcomes and measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality.

Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%).

Conclusions and relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold.

Trial registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Nogueira reported receiving consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Imperative Care, Medtronic, Phenox, Prolong Pharmaceuticals, and Stryker Neurovascular and having stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, and Perfuze. No other disclosures were reported.

Figures

Figure 1.. Eligibility, Randomization, and Follow-up of Patients Through the DEVT Randomized Clinical Trial of Intravenous Alteplase in Patients With Acute Ischemic Stroke

aOne patient had expanded Thrombolysis in Cerebral Infarction (eTICI) 3 on the first intracranial angiography; the other, eTICI 2c on first intracranial angiography. One patient withdrew immediately after randomization. bOne patient had eTICI 2c on first intracranial angiography; 2 had eTICI 2b on first intracranial angiography. cOf the survivors, 91 had video recording, 4 had voice recording, 1 outcome determined by local investigators blinded to the treatment assignments because video or voice recording was unavailable. dOf the survivors, 95 had video recording, 2 had voice recording, 0 outcomes determined by local investigators blinded to the treatment assignments. DEVT indicates Direct Endovascular Thrombectomy vs Combined IV Thrombolysis and Endovascular Thrombectomy for Patients With Acute Large Vessel Occlusion in the Anterior Circulation Trial; IV indicates intravenous; rt-PA, recombinant tissue type plasminogen activator.

Figure 2.. Distribution of the Modified Rankin Scale Score at 90 Days

Shown are scores on the modified Rankin Scale for patients in each group who were evaluated by means of video (186 patients) and voice (6 patients) recordings and by local investigators (1 patient). Forty-one patients died before 90 days. IV indicates intravenous.