Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for AIS in the Posterior Circulation: The IAT-TOP Randomized Clinical Trial

后循环急性缺血性卒中血栓切除术后动脉内阿替普酶溶栓治疗:IAT-TOP随机临床试验

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Abstract

IMPORTANCE: The impact of adjunctive intra-arterial alteplase after successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the posterior circulation requires further investigation. OBJECTIVE: To assess the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, prospective, randomized, open-label, blinded-end point (PROBE design) clinical trial. The study was conducted between September 5, 2023, and November 29, 2024, with the 3-month follow-up completed on February 18, 2025. The trial was conducted in 37 comprehensive stroke centers in China. Patients in China with acute basilar artery occlusion presenting within 24 hours of the time last known well were randomly assigned to the treatment group or control group. Eligible participants were adults who achieved successful recanalization after EVT. INTERVENTIONS: Eligible patients were randomly assigned to the intra-arterial alteplase group (0.225 mg/kg, maximum dose limit 22.5 mg infused at a concentration of 1.0 mg/mL within 15 minutes distal to the origin of posterior inferior cerebellar artery) or control group (no intra-arterial thrombolysis). MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the proportion of patients achieving functional independence (modified Rankin Scale score of 0-2) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours. RESULTS: A total of 247 patients were enrolled, and 1 patient was excluded from the full analysis set due to basilar artery reocclusion before intra-arterial alteplase. The remaining 246 patients (median [IQR] age, 65.0 [56.0-72.0] years; 176 male [71.5%]) were included in this analysis, 124 (50.4%) in the treatment group and 122 (49.6%) in the control group. Among the patients recruited and followed up, functional independence at 90 days was achieved in 52 (41.9%) in the intra-arterial alteplase group and 57 (46.7%) in the control group (adjusted risk ratio, 0.93; 95% CI, 0.73-1.18; P = .55). Mortality at 90 days (29.6% vs 27.0%, respectively; adjusted hazard ratio, 1.07; 95% CI, 0.71-1.61; P = .75) and incidence of symptomatic intracranial hemorrhage (2.4% vs 2.5%, respectively; unadjusted risk ratio, 0.98; 95% CI, 0.20-4.74; P = .97) were similar across groups. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial reveal that in patients with posterior circulation stroke due to acute basilar artery occlusion, intra-arterial alteplase after successful endovascular recanalization appeared to be safe but was not associated with improvement of functional outcomes at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05897554.

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