Intravenous Tenecteplase Research Articles

Efficacy and Safety of Intravenous Tenecteplase Before Endovascular Thrombectomy for Acute Ischemic Stroke: The Multicenter, Randomized, BRIDGE-TNK Trial Protocol.

Six randomized trials have not detected a difference between intravenous alteplase plus endovascular thrombectomy and endovascular thrombectomy alone in stroke. Tenecteplase, a recombinant human tenecteplase tissue-type plasminogen activator, is a genetically modified variant of alteplase. It is unclear whether the outcomes are different if alteplase is replaced with tenecteplase. This trial aims to determine whether intravenous tenecteplase within 4.5 hours of time last known well confers benefit in patients with acute ischemic stroke with large-vessel occlusion who undergo endovascular thrombectomy. BRIDGE-TNK (Thrombectomy With Versus Without rhTNK-tPA in Stroke) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded end point evaluation conducted at 40 thrombectomy-capable centers in China. This trial will randomize 544 patients with intravenous thrombolysis-eligible stroke (272 in each arm) with large-vessel occlusion within 4.5 hours of last known well to receive bridging intravenous tenecteplase with endovascular thrombectomy (tenecteplase-plus-thrombectomy group) or endovascular thrombectomy alone (thrombectomy-alone group). The primary outcome is the proportion of patients achieving functional independence, defined as a score of 0 to 2 on the modified Rankin Scale, at 90 days. Safety will be assessed via symptomatic intracranial hemorrhage at 48 hours and death at 90 days. BRIDGE-TNK will provide important data on the role of intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke with large-vessel occlusion who can be treated within 4.5 hours of last known well. URL: https://clinicaltrials.gov. Unique identifier: NCT04733742.

Efficacy and Safety of Intravenous Tenecteplase Versus Alteplase in Treating Acute Ischemic Stroke With Diabetes and Admission Hyperglycemia.

The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status. This was a post hoc analysis of the TRACE-2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0-1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran-Mantel-Haenszel χ2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes (P=0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes (P=0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P = 0.44; 65.4% versus 60.4%, P=0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia. This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status. URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Trans-Clot MAP gradient: A novel innovative technique during thrombectomy for acute ischemic stroke with potential applications for assessing collateral circulation, determining clot etiology, informing device selection, and predicting first-pass success.

Endovascular mechanical thrombectomy has significantly improved recovery in acute ischemic stroke (AIS). While traditional patient selection has relied on factors such as last known well and penumbra volume, emerging research highlights the importance of collateral circulation in influencing thrombectomy success. However, current methods to assess collateral circulation are often unreliable and lack standardization, limiting their integration into clinical decision-making and prompting the need for innovative approaches. This study introduces trans-clot manometry as a promising approach for quantitatively assessing collateral blood flow before thrombectomy. Two patients were included in this study: a 64-year-old female with a left M1 near-complete occlusion and an 81-year-old male with a left P1 occlusion. After receiving intravenous tenecteplase, each patient underwent emergent thrombectomy where intraoperative trans-clot manometry revealed significant trans-clot mean arterial pressure (MAP) gradients (66.7% for Patient 1 and 96.9% for Patient 2). Both patients had successful first-pass thrombectomy (Patient 1: TICI 3; Patient 2: TICI 3), with substantial clinical improvement (Patient 1: NIHSS 11 to 1; Patient 2: NIHSS 19 to 8). Intraoperative trans-clot manometry offers a simple yet powerful, objective, and generalizable measure of collateral circulation, applicable to a wide range of AIS cases regardless of clot location or vessel size. In addition, real-time correlations with heart-rate variability and radial artery pressures provide an intrinsic quality control, ensuring proper execution of the technique and accuracy of the resulting MAP gradient. Future research will focus on validating this approach, determining its generalizability, and establishing MAP gradient thresholds to enhance device selection and predict first-pass success.

Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke: The ORIGINAL Randomized Clinical Trial.

Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited. To establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset. The ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement. Patients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg). The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality. Among the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23]). In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting. ClinicalTrials.gov Identifier: NCT04915729.

The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT trial.

Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase. Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0-4 vs 5-7 vs 8-10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65-84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17-19)) with anterior circulation stroke were included. mRS 0-1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0-4, 5-7, and 8-10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes. Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase. Data shall made available on reasonable request from the PI (BMM).

Intravenous alteplase versus tenecteplase in patients with acute posterior circulation strokes: A secondary analysis from the AcT randomized controlled trial

ObjectivesThere are limited data available demonstrating the safety and efficacy of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke in the posterior circulation. Materials and methodsThis is a post-hoc analysis of the Alteplase compared to Tenecteplase (AcT) pragmatic, phase 3, registry-linked randomized controlled trial. Patients with any posterior circulation vessel occlusion on baseline imaging were included. Study outcomes included 90-day modified Rankin Scale (mRS) 0-1, mRS 0-2, ordinal mRS, death within 90 days, 24 h symptomatic intracerebral haemorrhage (sICH) and successful reperfusion/recanalization. Mixed effects regression adjusting for age, sex and stroke severity was used to analyze differences in outcomes between patients administered tenecteplase vs. alteplase. Further, sensitivity analysis was conducted for basilar artery occlusion (BAO) alone. ResultsOf 1577 patients, 136 (8.6 %, 77:alteplase, 59:tenecteplase) had posterior circulation stroke. Baseline characteristics were similar[median age 71 (IQR 60-81) vs. 72 (IQR 65-82) years, 57.1 % vs. 67.8 % males, median baseline NIHSS 7 (IQR 4-12) vs. 7 (IQR 4-16) in alteplase vs. tenecteplase arms, respectively]. 28 patients (20.6 %, 16:alteplase, 12:tenecteplase arm) underwent EVT. The median 90-120 days mRS was 2 (IQR 1-4). There were no differences between alteplase and tenecteplase for 90-d mRS 0-1 (adjRR 0.93;95 %CI 0.63-1.36), 90-day mRS 0-2 (adjRR 0.95; 95 %CI 0.72-1.26), sICH (RR 0.65; 95 %CI 0.06-7.02) and mortality (RR 1.21; 95 %CI 0.61-2.38). Successful reperfusion eTICI 2b-3 and successful recanalization rAOL 2b-3 was achieved in 23/28 (82 %, 12:alteplase, 11:tenecteplase) and in 16/28 (57 %, 14:alteplase, 12:tenecteplase), respectively. Similar results were seen in 31 patients (22.8 %) with BAO. ConclusionIntravenous tenecteplase has a similar effect on outcome as alteplase, without increased safety concerns in patients with acute posterior circulation strokes.

Number needed to treat with intravenous tenecteplase to reduce the need for mechanical thrombectomy in large vessel occlusion acute ischemic stroke patients: A retrospective look at real-world experience data

ObjectiveWe sought to describe short term outcomes in patients with large vessel occlusion acute ischemic stroke (LVOAIS) who were treated with intravenous tenecteplase (TNK) as compared to alteplase (tPA), focusing on reduction in the need for mechanical thrombectomy (MT). BackgroundIn LVOAIS, TNK has shown improved reperfusion and outcomes with a similar safety profile to tPA. Ultra-early reperfusion has been described with TNK which would prevent the need for MT. We analyze the magnitude of this effect in a “real-world” setting. Design/MethodsIn this retrospective study, demographic, clinical, and imaging information from patients with LVOAIS treated with intravenous thrombolysis was collected. Data was compared between the group treated with TNK and tPA. ResultsOne hundred eighty-six patients met the criteria for the study. Of these,144patients received tPA and 42 received TNK. Nine had clinical improvement prior to groin puncture and did not require angiography.When combining the number of patients who had recanalization on angiography before MT and those who had clinical improvement prior to angiography, there were a total of 23 patients. This was noted in 9.7 % of patients who received tPA and 21.4 % of those who received TNK (p = 0.043). For patients treated with TNK we observed a rapid clinical improvement, improved NIHSS, improved functional outcomes and decreased length of stay compared to patients treated with tPA. For patients with spontaneous recanalization either angiographically or with clinical improvement from intravenous thrombolysis, MT may not be required. ConclusionsIntravenous TNK in patients with LVOAIS decreases the need for MT, and is associated with improved outcomes and reduced length of stay.

Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial

Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. This international, multicentre, open-label, parallel-group, randomised, clinical non-inferiority trial enrolled patients from 35 hospitals in eight countries. Participants were aged 18 years or older, within 4·5 h of ischaemic stroke onset or last known well, were not being considered for endovascular thrombectomy, and met target mismatch criteria on brain perfusion imaging. Patients were randomly assigned (1:1) by use of a centralised web server with randomly permuted blocks to intravenous tenecteplase (0·25 mg/kg) or alteplase (0·90 mg/kg). The primary outcome was the proportion of patients without disability (modified Rankin Scale 0-1) at 3 months, assessed via masked review in both the intention-to-treat and per-protocol populations. We aimed to recruit 832 participants to yield 90% power (one-sided alpha=0·025) to detect a risk difference of 0·08, with an absolute non-inferiority margin of -0·03. The trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000243718, and the European Union Clinical Trials Register, EudraCT Number 2015-002657-36, and it is completed. Recruitment ceased early following the announcement of other trial results showing non-inferiority of tenecteplase versus alteplase. Between March 21, 2014, and Oct 20, 2023, 680 patients were enrolled and randomly assigned to tenecteplase (n=339) and alteplase (n=341), all of whom were included in the intention-to-treat analysis (multiple imputation was used to account for missing primary outcome data for five patients). Protocol violations occurred in 74 participants, thus the per-protocol population comprised 601 people (295 in the tenecteplase group and 306 in the alteplase group). Participants had a median age of 74 years (IQR 63-82), baseline National Institutes of Health Stroke Scale score of 7 (4-11), and 260 (38%) were female. In the intention-to-treat analysis, the primary outcome occurred in 191 (57%) of 335 participants allocated to tenecteplase and 188 (55%) of 340 participants allocated to alteplase (standardised risk difference [SRD]=0·03 [95% CI -0·033 to 0·10], one-tailed pnon-inferiority=0·031). In the per-protocol analysis, the primary outcome occurred in 173 (59%) of 295 participants allocated to tenecteplase and 171 (56%) of 306 participants allocated to alteplase (SRD 0·05 [-0·02 to 0·12], one-tailed pnon-inferiority=0·01). Nine (3%) of 337 patients in the tenecteplase group and six (2%) of 340 in the alteplase group had symptomatic intracranial haemorrhage (unadjusted risk difference=0·01 [95% CI -0·01 to 0·03]) and 23 (7%) of 335 and 15 (4%) of 340 died within 90 days of starting treatment (SRD 0·02 [95% CI -0·02 to 0·05]). The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible. Australian National Health Medical Research Council; Boehringer Ingelheim.

Intravenous tenecteplase for acute ischemic stroke between 4.5 and 6 h of onset (EXIT-BT2): Rationale and Design

Rationale: To date, the benefit of intravenous thrombolysis for acute ischemic stroke (AIS) patients without advanced neuroimaging selection is confined to within 4.5 h of onset. Our phase II EXIT-BT (Extending the tIme window of Thrombolysis by ButylphThalide up to 6 h after onset) trial suggested the safety, feasibility, and potential benefit of intravenous tenecteplase (TNK) in AIS between 4.5 and 6 h of onset. The EXIT-BT2 trial is a pivotal study undertaken to confirm or refute this signal. Aim: To investigate the efficacy and safety of TNK for AIS between 4.5 and 6 h of onset with or without endovascular treatment. Sample size estimates: A maximum of 1440 patients are required to test the superiority hypothesis with 80% power according to a two-sided 0.05 level of significance, stratified by age, sex, history of diabetes, location of vessel occlusion, baseline National Institute of Health stroke scale score, stroke etiology, and plan for endovascular treatment. Design: EXIT-BT2 is a prospective, randomized, open-label, blinded assessment of endpoint (PROBE), and multi-center study. Eligible AIS patients between 4.5 and 6 h of onset are randomly assigned 1:1 into a TNK group or control group. The TNK group will receive TNK (0.25 mg/kg, a single bolus over 5–10 s, maximum 25 mg). The control group will receive standard medical care in compliance with national guidelines for acute ischemic stroke. Both groups will receive standard stroke care from randomization to 90 days after stroke onset according to national guidelines. Outcome: The primary efficacy endpoint is excellent functional outcome, defined as a modified Rankin Scale score 0–1 at 90 days after randomization, while the primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾4 caused by intracranial hemorrhage within 24 (−6/+12) h after randomization. Conclusions: The results of EXIT-BT2 may determine whether intravenous TNK has a favorable risk/benefit profile in AIS between 4.5 and 6 h of onset.

Tenecteplase Versus Alteplase in Medium Vessel Occlusion Ischemic Stroke: A Secondary Analysis of the Alteplase Compared to Tenecteplase Randomized Trial.

The safety and efficacy of tenecteplase in patients with ischemic stroke due to medium vessel occlusion (MeVO) are not well studied. We aimed to compare tenecteplase with alteplase in stroke due to MeVO. Patients with baseline M2-middle cerebral artery (MCA), M3/M4-MCA, P2/P3/P4-posterior cerebral artery (PCA), A2/A3/A4-anterior cerebral artery (ACA) occlusions from the Alteplase Compared to Tenecteplase (AcT) trial were included. Primary outcome was the proportion of 90-day modified Rankin Scale (mRS) 0-1. Secondary outcomes were 90-day mRS 0-2, ordinal mRS, mortality, quality of life measures (EuroQol 5-Dimension 5-Level, EuroQol visual analog scale), and symptomatic intracerebral hemorrhage (sICH). Initial and final successful reperfusion were reported in patients undergoing endovascular thrombectomy (EVT). Among 1,558 patients with available baseline computed tomography angiography; 455 (29.2%) had MeVO of which 27.5% (125/455) were proximal M2; 16.3% (74/455) were distal M2; 35.2% (160/455) were M3/M4; 7.5% (34/455) were A2/A3/A4; and 13.6% (62/455) were P2/P3/P4 occlusions. EVT was performed in 87/455 (19.1%) patients. mRS 0-1 at 90 days was achieved in 37.9% in the tenecteplase versus 34.7% in the alteplase group (adjusted risk ratio [aRR] 1.07; 95% confidence interval [CI] 0.91-1.25). Rates of 90-day mRS 0-2, sICH, and mortality were similar in both groups. No statistical difference was noted in initial successful reperfusion rates (13.0% vs. 7.5%) among the 87 patients who underwent endovascular thrombectomy. However, final successful reperfusion was higher in the tenecteplase group (71.7% vs. 60.0%, aRR 1.29, 95% CI 1.04-1.61). Intravenous tenecteplase had comparable safety, functional outcomes and quality of life compared to intravenous alteplase among patients with MeVO. Among those treated with EVT, tenecteplase was associated with higher successful reperfusion rates than alteplase.

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke with Proven Occlusion (TEMPO-2): Rational and design of a multicenter, randomized open-label clinical trial.

Almost half of acute ischemic stroke patients present with mild symptoms and there are large practice variations in their treatment globally. Individuals with an intracranial occlusion who present with minor stroke are at an increased risk of early neurological deterioration and poor outcomes. Individual patient data meta-analysis in the subgroup of patients with minor deficits showed benefit of alteplase in improving outcomes; however, this benefit has not been seen with intravenous alteplase in published randomized trials. TEMPO-2 (A Randomized Controlled Trial of Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) is a prospective, open label with blinded outcome assessment, randomized controlled trial, designed to test the superiority of intravenous tenecteplase (0.25 mg/kg) over nonthrombolytic standard of care, with an estimated sample size of 1274 patients. Adult patients presenting with acute ischemic stroke with the National Institutes of Health Stroke Scale (NIHSS) ⩽ 5 and visible arterial occlusion or perfusion deficit within 12 h of onset are randomized to receive either tenecteplase (0.25 mg/kg) or standard of care. The primary outcome is return to baseline neurological functioning, measured by the modified Rankin scale (mRS) at 90 days. Safety outcomes include death and symptomatic hemorrhage (intra or extra-cranial). Other secondary outcomes include mRS 0-1, mRS 0-2, ordinal shift analysis of the mRS, partial, and full recanalization on follow-up computed tomography angiogram. Results of this trial will aid in determining whether there is benefit of using tenecteplase (0.25 mg/kg) in treating patients presenting with minor stroke who are at high risk of developing poor outcomes due to presence of an intracranial occlusion. Data will be available upon reasonable request.

AcT: Intravenous Tenecteplase Compared to Alteplase for Acute Ischaemic Stroke in Canada

AcT: Intravenous Tenecteplase Compared to Alteplase for Acute Ischaemic Stroke in Canada In this article, we detail the trial’s design and important clinical findings.

Case report: Tenecteplase for acute ischemic stroke after heparin reversal

Intravenous thrombolysis can be administered to appropriate patients with suspected acute ischemic strokes who are on intravenous heparin infusions after its rapid reversal with protamine sulfate. Several case reports suggest the safety of tissue-type plasminogen activator, or alteplase, in these scenarios. Noting the increasing preferential use of tenecteplase over alteplase for intravenous thrombolysis of acute ischemic stroke, the safe and efficacious use of tenecteplase following heparin reversal has not been demonstrated in the literature. Our case demonstrates successful use of intravenous tenecteplase in a patient who was anticoagulated with therapeutic heparin. The patient had no hemorrhagic complications and had an excellent neurological outcome.

Effect of continuous 2MHz transcranial ultrasound as an adjunct to tenecteplase thrombolysis in acute anterior circulation ischemic stroke patients: an open labeled non-randomized clinical trial.

The treatment of acute ischemic stroke has improved in last few decades. While meta-analyses of several trials have established the safety and efficacy of Intravenous (IV) Tenecteplase thrombolysis, concomitant continuous transcranial doppler (TCD) ultrasound administration has not been assessed in any clinical trial. The aim of this study was to determine the effects of continuous 2MHz TCD ultrasound during IV Tenecteplase thrombolysis for Middle cerebral artery (MCA) stroke. A total of 19 patients were included, 13 received TCD ultrasound and 6 sham TCD with IV Tenecteplase. TCD spectrum and difference in Pre and post TCD parameters were measured. Asymptomatic hemorrhagic transformation of infarct wasseen in two patients. There was no mortality or clinical worsening in thesonothrombolysis group as against sham sonothrombolysis group. Median of peak systolic velocity wasincreased in both thesonothrombolysis (P = 0.0002) and sham sonothrombolysis group (P-value = 0.001). The difference in change in mean flow velocity between two groups, sonothrombolysis (11cm/sec)and sham sonothrombolysis (3.5cm/sec) were also significantly different (P = 0.014). This pilot work has established safety of continuous 30min TCD application along with IV Tenecteplase thrombolysis and it concludes thatconcomitant 2MHz TCD ultrasound administration significantly increased the MCA blood flow compared to chemothrombolysis alone.CTRI Registered Number: CTRI/2021/02/031418.

Abstract WP6: Safety Outcomes of Intravenous Tenecteplase in Tandem Occlusions Undergoing Mechanical Thrombectomy With Acute Stenting

Background: Studies have demonstrated that the addition of alteplase for patients with tandem lesions who underwent mechanical thrombectomy and acute stenting was safe with improved outcomes. We aimed to assess the safety and efficacy of Intravenous Tenecteplase (IV TNK) for patients with tandem lesions who undergo mechanical thrombectomy (MT) and acute stenting. Methods: Using a prospectively collected registry of stroke patients seen at our institution we identified patients who underwent mechanical thrombectomy and acute carotid stenting between January 2021 and May 2023. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2 (PH-2). Secondary outcomes included favorable functional outcome (90-day modified Ranking score 0-2), 90-day mortality, successful reperfusion (modified Thrombolysis in Cerebral Infarction [TICI] score 2b-3) and median number of passes used. Outcomes were adjusted for age, NIHSS, ASPECTS, and last known well (LKW) time to arrival time. Results: A total of 86 patients were included of which 14 received IV TNK + MT with carotid stenting and 72 MT with carotid stenting alone. Patients who received IV TNK had lower median LKW to arrival time in minutes (133 [IQR 81-193] vs 575 [IQR 313-925], P&lt;0.001), and had higher ASPECTS median score (9 [9-10] vs 8 [7-9], P=0.03). There was 0% sICH vs 13.3% (p=0.36), and 0% PH-2 vs 4.2% (p&gt;0.999) in the IV TNK and the MT alone group, respectively. All patients who received tnk received intraprocedural eptifibatide loading dose and dual antiplatelets within 24 hours. Favorable functional outcomes were seen in 80.0% of IV TNK vs 58.2% of MT with carotid stenting alone (aOR 6.92 [0.45-105.7], p=0.16). Both groups had similar 90-day mortality rates 10% vs 9.1% (aOR 0.59 [0.01-34.9], p=0.8), number of passes 1 [1-2] vs 2 [1-3], (P=0.09), and successful reperfusion (TICI score 2b-3) 100% vs 98.6% (p&gt;0.999). Conclusion: Our study shows that the combination of IV TNK and MT with acute stenting for tandem lesions did not increase the risk of sICH or PH-2. IV TNK group did not have statistically significant differences in our secondary outcomes as well. However, the sample size was low, and this patient population needs to be studied in a larger group.

Abstract WP29: Early Adopter of Intravenous Tenecteplase: Two Year Clinical Experience in a Non-Academic Suburban Comprehensive Stroke Center for Acute Ischemic Stroke Treatment

Background: The most recent American Heart Association/American Stroke Association acute ischemic stroke guidelines recognize tenecteplase (TNK) as an alternative to alteplase (ALT) for acute ischemic stroke (AIS) treatment. TNK has a longer half-life, and is given as a single intravenous bolus compared to the complex and cumbersome ALT administration. A switch to TNK was implemented at our Comprehensive Stroke center (CSC) after a rigorous training of nurses and providers on May 1, 2021. We sought to evaluate the comparative performance of two thrombolytics over the period of last two years of ALT and first two years on TNK use. Methods: This was a retrospective review of prospectively collected database of consecutive AIS patients treated with ALT between May 2019 to April 2021 and those who received TNK from May 2021 to April 2023 at our CSC. Data samples were analyzed with respect to baseline patient characteristics, stroke severity, Door to Needle (DTN) time, 90 day Modified Rankin Scores (MRS), complications, and cost savings. Statistical analyzes were used for between group comparisons (SPSS). Results: A total of 115 patients were treated with ALT and 134 - with TNK. There were no significant differences in baseline characteristics or stroke severity between the groups (mean NIHSS of 10 for both). The mean DTN was 53.0 minutes for ALT and 41.5 minutes for TNK (p&lt;0.001). There was a strong trend towards improved 90-day clinical outcomes for TNK-treated patients (mRS 2.5 vs 3.1, p=0.06). No significant differences in rates of symptomatic Intracerebral Hemorrhage (SICH) were observed between two groups (2.6% ALT vs 2.9% TNK). Estimated cost savings of TNK use over two year period were $75,102. Conclusion: Our real-world data suggests that intravenous TNK for AIS appears to be safe and may result in improved clinical outcomes and substantial cost savings compared to ALT.

Intravenous tenecteplase compared with alteplase for minor ischaemic stroke: a secondary analysis of the AcT randomised clinical trial

BackgroundIn ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and...

Outcomes associated to the time to treatment with intravenous tenecteplase for acute ischaemic stroke: subgroup analysis of the TRACE-2 randomised controlled clinical trial.

The benefit of intravenous alteplase in acute ischaemic stroke (AIS) is time-dependent. Tenecteplase is non-inferior to alteplase among patients with AIS. We aimed to delineate the association of the stroke onset to treatment time (OTT) with tenecteplase compared with alteplase on therapeutic benefit and clinical risks. This is a post hoc analysis of the Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-2 an open-label, randomised, controlled, non-inferior trial. A total of 1430 AIS within 4.5 hours onset at 53 sites in China from 12 June 2021 to 29 May 2022 were randomly assigned (1:1) to receive either tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale score of 0-1 at 90 days. A post hoc subgroup analysis was conducted with the OTT divided into three intervals (0-90 min, 91-180 min and 181-270 min). The primary safety outcome was symptomatic intracranial haemorrhage within 36 hours post-thrombolytic treatment. Treatment was initiated within 270 min of stroke onset in 1412 patients who were randomly allocated to either tenecteplase (n=707) or alteplase (n=705). The OR of primary efficacy outcome was similar as OTT increased (p=0.84). Adjusted odds of an excellent functional outcome were 0.99 (95% CI 0.37 to 2.67) for 0-90 min, 1.23 (95% CI 0.88 to 1.71) for 91-180 min and 1.21 (95% CI 0.88 to 1.65) for 181-270 min. All were in favour of the tenecteplase group. Meta-analysis of 2949 patients yielded a pooled risk difference of 5.54 (95% CI -0.18 to 11.26; p=0.82) in favour of tenecteplase for more than 180 min and 1.77 (95% CI -2.66 to 6.20; p=0.58) for 0-180 min. In AIS patients who were treated with either tenecteplase or alteplase within 4.5 hours onset, there was no difference observed in the efficacy and safety between the two groups at the three different OTT time intervals.

Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial

BackgroundThe performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the...