Dataset Information

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

ABSTRACT:

Importance

Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase.

Objective

To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke.

Design, setting, and participants

Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria.

Interventions

Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy.

Main outcomes and measures

The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death.

Results

All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]).

Conclusions and relevance

Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned.

Trial registration

ClinicalTrials.gov Identifier: NCT03340493.

SUBMITTER: Campbell BCV

PROVIDER: S-EPMC7139271 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Campbell Bruce C V BCV Mitchell Peter J PJ Churilov Leonid L Yassi Nawaf N Kleinig Timothy J TJ Dowling Richard J RJ Yan Bernard B Bush Steven J SJ Thijs Vincent V Scroop Rebecca R Simpson Marion M Brooks Mark M Asadi Hamed H Wu Teddy Y TY Shah Darshan G DG Wijeratne Tissa T Zhao Henry H Alemseged Fana F Ng Felix F Bailey Peter P Rice Henry H de Villiers Laetitia L Dewey Helen M HM Choi Philip M C PMC Brown Helen H Redmond Kendal K Leggett David D Fink John N JN Collecutt Wayne W Kraemer Thomas T Krause Martin M Cordato Dennis D Field Deborah D Ma Henry H O'Brien Bill B Clissold Benjamin B Miteff Ferdinand F Clissold Anna A Cloud Geoffrey C GC Bolitho Leslie E LE Bonavia Luke L Bhattacharya Arup A Wright Alistair A Mamun Abul A O'Rourke Fintan F Worthington John J Wong Andrew A AA Levi Christopher R CR Bladin Christopher F CF Sharma Gagan G Desmond Patricia M PM Parsons Mark W MW Donnan Geoffrey A GA Davis Stephen M SM

JAMA 20200401 13

<h4>Importance</h4>Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase.<h4>Objective</h4>To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke.<h4>Design, setting, and participants</h4>Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using o ...[more]

PMID: 32078683

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Project description:IntroductionIn intracranial medium-vessel occlusions (MeVOs), intravenous thrombolysis (IVT) shows inconsistent effectiveness and endovascular interventions remains unproven. We evaluated a new therapeutic strategy based on a second IVT using tenecteplase for MeVOs without early recanalization post-alteplase.Patients and methodsThis retrospective, comparative study included consecutively low bleeding risk MeVO patients treated with alteplase 0.9 mg/kg at two stroke centers. One center used a conventional single-IVT approach; the other applied a dual-IVT strategy, incorporating a 1-h post-alteplase MRI and additional tenecteplase, 0.25 mg/kg, if occlusion persisted. Primary outcomes were 24-h successful recanalization for efficacy and symptomatic intracranial hemorrhage (sICH) for safety. Secondary outcomes included 3-month excellent outcomes (modified Rankin Scale score of 0-1). Comparisons were conducted in the overall cohort and a propensity score-matched subgroup.ResultsAmong 146 patients in the dual-IVT group, 103 failed to achieve recanalization at 1 h and of these 96 met all eligible criteria and received additional tenecteplase. Successful recanalization at 24 h was higher in the 146 dual-IVT cohort patients than in the 148 single-IVT cohort patients (84% vs 61%, p < 0.0001), with similar sICH rate (3 vs 2, p = 0.68). Dual-IVT strategy was an independent predictor of 24-h successful recanalization (OR, 2.7 [95% CI, 1.52-4.88]; p < 0.001). Dual-IVT cohort patients achieved higher rates of excellent outcome (69% vs 44%, p < 0.0001). Propensity score matching analyses supported all these associations.ConclusionIn this retrospective study, a dual-IVT strategy in selected MeVO patients was associated with higher odds of 24-h recanalization, with no safety concerns. However, potential center-level confounding and biases seriously limit these findings' interpretation.Trial registrationClinicalTrials.gov Identifier: NCT05809921.

Project description:Background: Whether bridging treatment combining intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) is superior to direct EVT alone for emergent large vessel occlusion (LVO) in the anterior circulation is unknown. A systematic review and a meta-analysis were performed to investigate and assess the effect and safety of bridging treatment vs. direct EVT in patients with LVO in the anterior circulation. Methods: PubMed, EMBASE, and the Cochrane library were searched to assess the effect and safety of bridging treatment and direct EVT in LVO. Functional independence, mortality, asymptomatic and symptomatic intracranial hemorrhage (aICH and sICH, respectively), and successful recanalization were evaluated. The risk ratio and the 95% CI were analyzed. Results: Among the eight studies included, there was no significant difference in the long-term functional independence (OR = 1.008, 95% CI = 0.845-1.204, P = 0.926), mortality (OR = 1.060, 95% CI = 0.840-1.336, P = 0.624), recanalization rate (OR = 1.015, 95% CI = 0.793-1.300, P = 0.905), and the incidence of sICH (OR = 1.320, 95% CI = 0.931-1.870, P = 0.119) between bridging therapy and direct EVT. After adjusting for confounding factors, bridging therapy showed a lower recanalization rate (effect size or ES = -0.377, 95% CI = -0.684 to -0.070, P = 0.016), but there was no significant difference in the long-term functional independence (ES = 0.057, 95% CI = -0.177 to 0.291, P = 0.634), mortality (ES = 0.693, 95% CI = -0.133 to 1.519, P = 0.100), and incidence of sICH (ES = -0.051, 95% CI = -0.687 to 0.585, P = 0.875) compared with direct EVT. Meanwhile, in the subgroup analysis of RCT, no significant difference was found in the long-term functional independence (OR = 0.927, 95% CI = 0.727-1.182, P = 0.539), recanalization rate (OR = 1.331, 95% CI = 0.948-1.867, P = 0.099), mortality (OR = 1.072, 95% CI = 0.776-1.481, P = 0.673), and sICH incidence (OR = 1.383, 95% CI = 0.806-2.374, P = 0.977) between patients receiving bridging therapy and those receiving direct DVT. Conclusion: For stroke patients with acute anterior circulation occlusion and who are eligible for intravenous thrombolysis, there is no significant difference in the clinical effect between direct EVT and bridging therapy, which needs to be verified by more randomized controlled trials.

Dataset Information

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

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