Intra-arterial tenecteplase is safe and may improve the first-pass recanalization for acute ischemic stroke with large-artery atherosclerosis: the BRETIS-TNK trial

Abstract

Background and purposeThe first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients.Materials and methodsThe BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4 mg/min) given continuously for 20 min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b.ResultsThe first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%, p = 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%, p = 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%, p = 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%, p = 0.11).ConclusionThis is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.

Benefit of endovascular treatment for primary versus secondary medium vessel occlusion: A multi‐center experience

“…Distal emboli occurred in 19.3% of MCA patients in our study, which was higher than that reported in previous studies 34 . It is noteworthy that secondary MeVO had poorer outcomes compared with LVO, 13 suggesting the need for more effective EVT methods to achieve complete recanalization, such as intra‐arterial thrombolysis during EVT 35,36 …”

“…34 It is noteworthy that secondary MeVO had poorer outcomes compared with LVO, 13 suggesting the need for more effective EVT methods to achieve complete recanalization, such as intra-arterial thrombolysis during EVT. 35,36 The presence of LMC varied by the location of arterial occlusion and was associated with good outcomes. [37][38][39] In this study, the proportion of LMC in patients with primary MeVO was significantly lower than that in patients with secondary MeVO (23% vs. 45%).…”

No-Reflow Post-Recanalization in Acute Ischemic Stroke: Mechanisms, Measurements, and Molecular Markers

“…They hypothesized that immediate thrombolytic agent after MT would be important to reduce the risk of secondary MT and associated microembolization and endothelial injury. 71 Functional independence between treatment and control groups was not statistically significant. Here, multiple groups have attempted to treat only one of the 3 potential mechanisms of no-reflow.…”

“…Specifically, they found that patients treated with adjunct alteplase were significantly more likely to have an mRS score of 0 or 1 at 90 days compared with their control group. 70 Zhao et al 71 followed a similar paradigm but instead delivered intraarterial tenecteplase immediately following first-attempt MT. They hypothesized that immediate thrombolytic agent after MT would be important to reduce the risk of secondary MT and associated microembolization and endothelial injury.…”

Intra-arterial tenecteplase during thrombectomy for acute stroke (BRETIS-TNK II): rationale and design

“…The hypothesis was supported by our recent BRETIS-TNK study, which was a prospective, single-arm, single-centre study, indicating that intra-arterial TNK administration as an adjunct to mechanical thrombectomy seemed safe and feasible, with the potential to increase first-pass reperfusion rates (53.8% vs 36.0%) and good clinical outcome (50% vs 34.6%), compared with historical control patients. 13 Based on these pilot results, we designed this trial to determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients.…”