Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy: The ANGEL-TNK Randomized Clinical Trial.

Abstract

IMPORTANCE The role of intra-arterial tenecteplase for acute large vessel occlusion (LVO) stroke after successful endovascular therapy is uncertain. OBJECTIVE To assess the efficacy and safety of intra-arterial tenecteplase in patients with successful endovascular therapy (defined as a score on the expanded Thrombolysis in Cerebral Infarction [eTICI] scale of 2b to 3) after endovascular therapy. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, open-label, blinded end point, randomized trial. Recruitment took place between February 16, 2023, and March 23, 2024, with final follow-up on July 4, 2024. The study was conducted across 19 centers in China. Patients with acute anterior circulation LVO treated between 4.5 and 24 hours from the time that the patient was last known to be well were included. INTERVENTION After successful endovascular recanalization, defined as eTICI 2b or greater, patients were randomized to receive intra-arterial tenecteplase at 0.125 mg/kg (n = 126) or standard medical treatment (n = 129). MAIN OUTCOMES AND MEASURES The primary end point was excellent outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0 to 1 (range, 0 [no symptoms] to 6 [death]). There were a total of 7 secondary efficacy end points (mRS score of 0-1 at 90 days, mRS score at 90 days, mRS score of 0-2 at 90 days, mRS score of 0-3 at 90 days, National Institutes of Health Stroke Scale score of 0-1 or improved ≥10 points at 36 hours, European Quality of Life Visual Analogue Scale score at 90 days, time to maximum volume > 6 s at 24 hours, and infarct core volume change from baseline) and 3 safety end points, including symptomatic intracranial hemorrhage (sICH) within 48 hours, any intracranial hemorrhage within 48 hours, and all-cause mortality within 90 days. RESULTS Among 256 patients who were randomized (median [IQR] age, 71.6 [61.3-79.2] years; 113 [44.1%] females), 255 (99.6%) completed the trial. The rate of patients with an mRS score of 0 to 1 at 90 days was 40.5% in the intra-arterial tenecteplase group (n = 51) and 26.4% in the standard medical treatment group (n = 34) (relative risk, 1.44 [95% CI, 1.06-1.95]; P = .02). Of 7 prespecified secondary efficacy end points, none showed a significant difference. Intra-arterial tenecteplase after endovascular therapy did not increase the incidence of sICH within 48 hours after treatment compared with standard medical treatment (5.6% vs 6.2%; relative risk, 0.95 [95% CI, 0.36-2.53]; P = .92). Mortality at 90 days was 21.4% with intra-arterial tenecteplase and 21.7% with standard medical treatment (relative risk, 0.76 [95% CI, 0.40-1.43]; P = .78). CONCLUSIONS AND RELEVANCE In patients with acute LVO presenting between 4.5 and 24 hours of symptom onset, intra-arterial tenecteplase after successful thrombectomy had a greater likelihood of excellent neurological outcome at 90 days without increasing the risk of sICH or mortality. However, because none of the secondary efficacy analyses supported the primary finding, further trials are needed to confirm the results. Trial Registration ClinicalTrials.gov Identifier: NCT05624190.