Tenecteplase In Acute Ischemic Stroke Research Articles

“Intraosseous administration of tenecteplase for thrombolysis of an acute ischemic stroke”

IntroCurrent guidelines for acute ischemic stroke recommend timely administration of intravascular thrombolytic therapy to promote functional and neurologic outcomes. Tenecteplase is an emerging off-label therapy for this indication and being utilized by various institutions due to its simpler administration strategy. In emergent situations in which intravenous access cannot be obtained, intraosseous access is a viable option for medication administration. However, there has been minimal published cases to support the efficacy and safety of intraosseous administration of tenecteplase for acute ischemic stroke. CaseWe describe the case of a 51-year-old woman who developed acute ischemic stroke within our institution. Due to difficulty achieving intravenous access and time-dependent efficacy of thrombolytic therapy, the decision was made to administer tenecteplase by the intraosseous route. Stroke symptoms improved within 48 hours following administration without complication. ConclusionIntraosseous administration of tenecteplase may be considered for treatment of acute ischemic stroke if intravenous access is unattainable.

Comparative efficacy and safety among different doses of tenecteplase for acute ischemic stroke: A systematic review and network meta-analysis

ObjectivesTenecteplase (TNK) is a promising alternative to alteplase (ALT) as the thrombolytic agent for acute ischemic stroke (AIS). However, its clinical outcomes in certain populations remain unclear. This study aimed to compare the efficacy and safety among different doses of TNK in AIS patients. MethodsWe searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Embase for studies comparing at least one dose of TNK to another dose of TNK or ALT 0.90 mg/kg. We conducted Bayesian network meta-analyses to estimate the relative risks (RRs) and 95% credible intervals (CrIs) for all outcomes using ALT 0.90 mg/kg as the reference. The treatments were ranked according to their surface under the cumulative ranking (SUCRA) values. ResultsWe included 11 trials from 16 publications comprising 5423 participants. There were no significant differences between any doses of TNK and ALT for reperfusion, 3-month modified Rankin Score (mRS) 0–1 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.68), mRS 0-2 (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.86), mortality (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.82), intracranial hemorrhage (ICH) (rank 1st: TNK 0.25 mg/kg; SUCRA = 0.88), symptomatic ICH (sICH) (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.70), and parenchymal hematoma (rank 1st: TNK 0.10 mg/kg; SUCRA = 0.68). TNK 0.40 mg/kg had a significantly higher sICH rate compared to TNK 0.25 mg/kg (RR = 2.39, 95% CrI = 1.00–7.92). Among elderly patients, TNK 0.25 mg/kg had a significantly lower rate of sICH than ALT 0.9 mg/kg (RR = 3.0 × 10-13, 95% CrI = 3.4 × 10-40–0.07). ConclusionsTNK has efficacy and safety outcomes comparable to those of ALT. TNK 0.25 mg/kg may be the optimal dose of TNK for patients with AIS.

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.

A Systematic Review of the Efficacy and Safety of Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Time to Pass the Torch

Alteplase, a biosynthetic form of human tissue‐type plasminogen activator, is Food and Drug Administration‐approved for the treatment of acute ischemic stroke and currently the standard of care for thrombolytic therapy. Tenecteplase, a modified form of alteplase using recombinant technology, has several pharmacological advantages over alteplase, including longer half‐life, higher fibrin specificity, and greater resistance to plasminogen activator inhibitor‐1. Additionally, tenecteplase is given as a single bolus administration compared to the bolus plus 1‐hour continuous infusion of alteplase. Given these pharmacologic and logistical differences along with studies demonstrating noninferiority compared with alteplase, tenecteplase has become an alternative thrombolytic for the management of acute ischemic stroke. There is a growing body of evidence that suggests tenecteplase is a safe and effective alternative to alteplase. This systematic review evaluates the available literature for the use of tenecteplase in acute ischemic stroke and provides relevant discussion regarding role in therapy, therapeutic strategies, and areas requiring further research.

Successful Use of Intraosseous Tenecteplase in Acute Ischemic Stroke (P9-5.007)

Successful Use of Intraosseous Tenecteplase in Acute Ischemic Stroke (P9-5.007)

Abstract TP66: Decreased Order to Administration Times Following Transition to Tenecteplase for Acute Ischemic Stroke

Introduction: Alteplase was the first approved tissue plasminogen activator and standard of care for acute ischemic stroke (AIS). The utilization of Tenecteplase as a thrombolytic agent in AIS has offered many organizations several advantages over Alteplase, including ease of preparation and administration. Both thrombolytic agents require a Physician's order and reconstitution by a certified Pharmacist or Registered Nurse prior to administration. Our academic comprehensive stroke center transitioned from Alteplase to Tenecteplase as standard thrombolysis for acute ischemic stroke in November 2022. Treatment times were monitored to explore the benefits of a single bolus administration. Methods: A retrospective chart review was conducted at a single academic comprehensive stroke center. Patients were included if they received thrombolytic therapy in the Emergency Department for a diagnosis of AIS. Patients prior to November 2022 received Alteplase, and those after November 2022 received Tenecteplase. We evaluated the time frame for the medication bolus order for Alteplase and Tenecteplase to the administration time. Results: Of 140 patients screened, 108 were included in the study, with 51 in the alteplase group and 57 in the Tenecteplase group. Mean order to administration times were 10.9 minutes in the alteplase group and 7.37 minutes in the Tenecteplase group, with statistical significance (P=0.0052). There was no significant difference in mean door-to-needle time (59.27 Alteplase vs 53.09 Tenecteplase, P= 0.1803). Conclusions: In a single CSC, the transition from Alteplase to Tenecteplase reduced the order to administration time by 3.53 minutes. The decreased administration time highlights one of Tenecteplase’s potential advantages. Further review is necessary to evaluate additional stroke metrics and clinical outcomes.

Tenecteplase, 0.4 mg/kg, in Moderate and Severe Acute Ischemic Stroke: A Pooled Analysis of NOR-TEST and NOR-TEST 2A.

Background The optimal dose of tenecteplase in acute ischemic stroke remains to be defined. We present a pooled analysis of the 2 NOR-TESTs (Norwegian Tenecteplase Stroke Trials) exploring the efficacy and safety of tenecteplase, 0.4 mg/kg. Methods and Results We retrospectively reviewed 2 PROBE (Prospective Randomized Open, Blinded End-point) trials, NOR-TEST and NOR-TEST 2A. Patients were randomized to either tenecteplase, 0.4 mg/kg, or alteplase, 0.9 mg/kg. The primary end point was favorable functional outcome at 3 months (modified Rankin Scale score, 0-1) or return to baseline if prestroke modified Rankin Scale score was 2. Secondary end points included favorable functional and clinical outcome and safety data. The pooled analysis includes patients with National Institutes of Health Stroke Scale score ≥6 from both trials and an additional post hoc analysis of patients with National Institutes of Health Stroke Scale score ≤5 from NOR-TEST. The per-protocol analysis contains 483 patients, of whom 235 were assigned to tenecteplase and 248 were assigned to alteplase. In per-protocol analysis, functional outcome was better in the alteplase arm with cutoff modified Rankin Scale score of 2 (odds ratio [OR], 0.52 [95% CI, 0.33-0.80]; P=0.003) and expressed by ordinal shift analysis (OR, 1.64 [95% CI, 1.17-2.28]; P=0.004). Mortality at 3 months was higher in the tenecteplase arm (OR, 2.48 [95% CI, 1.20-5.10]; P=0.01). Mortality and intracranial hemorrhage rates were higher in the severe stroke group randomized to tenecteplase, whereas these rates were similar for alteplase and tenecteplase in moderate and mild stroke. Conclusions Tenecteplase, 0.4 mg/kg, is unsafe in moderate and severe stroke, and the risk of death and intracranial hemorrhage probably increases with stroke severity. A lower tenecteplase dose should be tested in future trials. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01949948, NCT03854500.

Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS).

The aim of this study is to monitor, identify, and compare the adverse events (AEs) related to tenecteplase and alteplase, with the objective of exploring the potential safety of tenecteplase for acute ischemic stroke (AIS) and guiding its use to enhance patient safety. In order to evaluate the disproportionality of AEs associated with tenecteplase and alteplase in real-world data, four algorithms (ROR, PRR, BCPNN, EBGM) were utilized as measures to detect signals of AEs related to both drugs. Subsequently, Breslow-Day statistical analysis was applied to compare the RORs of the main system organ classes (SOCs) and key preferred terms (PTs) between tenecteplase and alteplase. A statistical analysis was performed utilizing data gleaned from the Food and Drug Administration Adverse Event Reporting System (FAERS) database, encompassing 19,514,140 case reports from 2004Q1 to 2023Q1. There were 1,004 cases where tenecteplase was reported as the primary suspected (PS) and 2,363 tenecteplase-related adverse drug reactions (ADRs) at the PTs level were identified, the two data of alteplase were 10,945 and 25,266, respectively. The occurrence of drug-induced ADRs was analyzed across 27 organ systems, The analysis revealed several expected ADRs, such as Haemorrhage, Hypersensitivity which were consistent with the two drug-labels. It is of note that the signal strengths of 'death,' 'ventricular fibrillation,' 'cardiogenic shock' and 'pneumonia aspiration' at the PT level were markedly higher for tenecteplase than for alteplase, whereas the signal strength of 'angioedema' at the PT level was significantly higher for alteplase in comparison to tenecteplase. Additionally, unexpected significant ADRs associated with ocular adverse reactions and pneumonia aspiration at the PT level were identified, indicating potential AEs not currently mentioned in the drug instructions. This study identified and compared signals of ADRs associated with tenecteplase and alteplase, although tenecteplase is as effective as alteplase and has advantages such as ease of use and affordability, it cannot replace alteplase in the treatment of AIS until its safety profile is fully recognized. Additionally, previously unreported ocular ADRs and pneumonia were identified, providing valuable insights into the relationship between ADRs and the use of these thrombolytic drugs. These findings underscore the importance of continuous monitoring and effective detection of AEs to ultimately enhance the safety of AIS patients undergoing thrombolytic therapy.

An Experience of a Single Comprehensive Stroke Center after Implementation of Routine Tenecteplase Administration for Acute Ischemic Stroke Treatment. (P7-5.023)

<h3>Objective:</h3> The objectives of this study were to determine if there is a significant difference between Alteplase and Tenecteplase in improvement of NIHSS, door to needle time (DTNT), disability at discharge determined by modified Rankin scale (mRS), and rate of intracranial hemorrhage (ICH). <h3>Background:</h3> There is growing interest in using Tenecteplase for acute ischemic stroke (AIS) treatment. Currently there is no clear consensus on its indication and dosage. We transitioned to Tenecteplase administration for AIS treatment in March 2021, at a dosage of 0.25 mg/kg. <h3>Design/Methods:</h3> A retrospective comparison analysis on the outcomes of AIS patients who were treated with Alteplase between April 2020 – March 2021 or Tenecteplase between April 2021 – March 2022. <h3>Results:</h3> Of 216 patients, 45.8% (n = 99) were given Alteplase and 54.1% (n = 117) were given Tenecteplase. There was no significant difference in baseline characteristics except hyperlipidemia, substance use, and history of smoking. No mean difference in mRS was measured at admission or discharge between Alteplase (1.42+/− 1.77) and Tenecteplase (1.32 +/− 1.56, p-value 0.703) and delta NIHSS between Alteplase and Tenecteplase (p-value 0.926). There was no difference in DTNT between both groups (p-value 0.172). Successful recanalization ratio was not significantly different. Symptomatic ICH was of no significant difference between the two groups: occurring in 5.05% patients receiving Alteplase and 5.13% patients receiving Tenecteplase (p-value 0.682). Rate of mortality was 13.13% (n = 13) in Alteplase and 11.11% (n = 13) in Tenecteplase, also of no significant difference (p-value 0.683). <h3>Conclusions:</h3> The results suggest that Tenecteplase has a similar efficacy and safety profile to Alteplase in real world practice. These findings are similar to results of previous randomized trials. At the dose of 0.25 mg/kg, Tenecteplase appears to be a reasonable alternative to Alteplase for use with acute ischemic strokes within 4.5 hours of onset. <b>Disclosure:</b> Dr. Cawley has nothing to disclose. Dr. Simon has nothing to disclose. Dr. Radomski has nothing to disclose. Dr. Kuns has nothing to disclose. Dr. Bejleri has nothing to disclose. Dr. Seol has nothing to disclose. Dr. Razak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals.

Use of Tenecteplase in Acute Ischemic Stroke in the Time of SARS-CoV-2.

Tenecteplase (TNK) is a fibrinolytic drug that is administrated in a single bolus, recommended in eligible patients with acute ischemic stroke prior to mechanical thrombectomy. This study explores its usefulness in adverse situations, such as the SARS-CoV-2 pandemic. We conducted a retrospective study involving consecutive patients with suspected acute ischemic stroke treated either with intravenous fibrinolysis with alteplase during 2019 or with TNK (.25 mg/kg) between March 2020 and February 2021. A comparative analysis was made to compare patient treatment times and prognosis. A total of 117 patients treated with alteplase and 92 with TNK were included. No significant differences were observed in age, main vascular risk factors or previous treatments. The median National Institutes of Health Stroke Scale was 8 in the alteplase group and 10 in those treated with TNK (P = .13). Combined treatment with mechanical thrombectomy was performed in 47% in the alteplase group and 46.7% in the TNK group; Thrombolysis In Cerebral Infarction scale 2b-3 recanalization was achieved in 83% and 90.7%, respectively (P = .30). There was a decrease in onset-to-needle median time (165min vs 140min, P < .01) and no significant variations in door-needle median time. There was no significant difference in the incidence of symptomatic hemorrhagic transformation in mortality or functional independence at 3months. The easier administration of TNK has improved the accessibility of fibrinolytic therapy, even in adverse circumstances, such as the COVID-19 pandemic. Its use appears to be safe and effective, even in patients who are not candidates for mechanical thrombectomy.

Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society.

Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS. Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved. A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion. These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.

806: SAFETY AND EFFICACY OF TENECTEPLASE IN ACUTE ISCHEMIC STROKE

806: SAFETY AND EFFICACY OF TENECTEPLASE IN ACUTE ISCHEMIC STROKE

Different dosing regimens of Tenecteplase in acute ischemic stroke: A network meta-analysis of the clinical evidence.

Acute ischemic stroke remains the major cause of death and disability and conclusive evidence of Tenecteplase in treating stroke is lacking. To conduct a meta-analysis to determine whether Tenecteplase produces better outcomes than Alteplase and a network meta-analysis comparing the different dosing regimens of Tenecteplase. Searches were made in MEDLINE, CENTRAL, and ClinicalTrials.gov. The outcome measures are recanalization, early neurological improvement, functional outcomes at 90 days (modified Rankin Scale 0-1 and 0-2), intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 days from treatment. Fourteen studies are included in the meta-analyses and 18 studies in the network meta-analyses. In the meta-analysis, Tenecteplase 0.25 mg/kg has significant results in early neurological improvement (OR = 2.35, and 95% CI = 1.16-4.72) and excellent functional outcome (OR = 1.20, and 95% CI = 1.02-1.42). In the network meta-analysis, Tenecteplase 0.25 mg/kg produces significant results in early neurological improvement (OR = 1.52 [95% CI = 1.13-2.05], p-value = 0.01), functional outcomes (mRS 0-1 and 0-2) (OR = 1.19 [95% CI = 1.03-1.37], p-value = 0.02; OR = 1.21 [95% CI = 1.05-1.39], p-value = 0.01; respectively) and mortality (OR = 0.78 [95% CI = 0.64-0.96], p-value = 0.02) whereas Tenecteplase 0.40 mg/kg increases the chances of symptomatic intracranial hemorrhage (OR = 2.35 [95% CI = 1.19-4.64], p-value = 0.01). While not conclusive, our study lends evidence to 0.25 mg/kg Tenecteplase dose for ischemic stroke treatment. Further randomized trials need to be done to validate this finding. International prospective register of systematic reviews (PROSPERO) - CRD42022339774URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339774.

The Use of Intravenous Tenecteplase in Acute Ischemic Stroke after Idarucizumab Reversal of Dabigatran Anticoagulant Effects; Experience from a Regional Hospital Directed by Video Telemedicine Stroke Specialist

Novel Oral Anticoagulants (NOACs) are widely used in patients with non-valvular atrial fibrillation to prevent Acute Ischemic Stroke (AIS) and other thrombo- embolic phenomena. The management of AIS with Intravenous Thrombolysis Therapy (IVT), also known as fibrinolytic therapy in people who are taking NOACs poses a great challenge due to increased risks of hemorrhage and intracranial bleeding. We present the case of a 77-year-old man on dabigatran for atrial fibrillation who woke up with an extensive right middle cerebral artery ischemic stroke and had his anticoagulant effects reversed with idarucizumab before successful thrombolysis with intravenous tenectaplase.

Abstract WMP29: “Good Times”: Has The Change From Tissue Plasminogen Activator To Tenecteplase For Acute Ischemic Stroke Improved Treatment Times?

Background: Stroke is the leading cause of disability and the 5th leading cause of death in the US. The advent of tissue plasminogen activator (TPA) was a game changer in the treatment of acute ischemic stroke. Today at Cedars Sinai Medical Center, we have implemented the use of Tenecteplase (TNK) for our Code Brain patients, a more cost-effective, easier- to- use thrombolytic. TNK is non- inferior to TPA and studies show a potential benefit in reperfusion of large vessel occlusions (NEJM, 2018). Hypothesis: To decrease the ED and inpatient door-to-needle (DTN) times, and thrombolytic with thrombectomy (bridge) door-to-groin (DTG) puncture times, by June 20, 2021 using TNK, as measured by data acquired 6 months prior to TNK implementation (July 20, 2020 through January 19, 2021) and data acquired 6 months after TNK implementation (January 20, 2021 through June 20, 2021). Implementation: We performed a retrospective chart review of times for patients who received TNK alone and: for those who received bridge therapy after TNK implementation. These times were compared with 6 months of data prior to TNK implementation. Results: Our review of the data revealed that the median times for ED DTN, in-house DTN and bridge DTP were 46, 61.5, and 98.5 minutes respectively. Data for six months after the implementation of TNK reveals that the median times for ED DTN, in-house DTN and bridge DTP were 48, 51.5, and 88 minutes respectively. Conclusions: We discovered that although ED DTN times were unremarkable, our in-house DTN times and bridge DTP times markedly improved. In fact, for the first time, we have surpassed the American Heart Association benchmark of 90 minutes DTP times. We conclude that TNK is easier to administer, more cost effective, and decreased our treatment times for our in-house Code Brain patients who received TNK alone and our Code brain patients who received bridge therapy. We will continue to track and trend this data and seek out areas of improvement.

A practice game changer: Impact of tenecteplase for acute ischemic stroke in a multicenter quality improvement project.

Tenecteplase is a thrombolytic that is more fibrin specific, has a longer half-life, and is easier to administer than alteplase for acute ischemic stroke (AIS). This article outlines the pharmacy experience and perspective on implementation of tenecteplase as the treatment of choice for AIS. Tenecteplase has been of increasing interest for AIS and is currently being studied in several clinical trials. Although it is not indicated by the Food and Drug Administration for AIS, several published studies and an update to stroke guidelines from the American Heart Association and American Stroke Association support its use in this setting. In January 2021, Cedars-Sinai Health System made the decision to add tenecteplase to the formulary for AIS in addition to keeping alteplase for patients who met the criterion of being outside the 4.5-hour window following stroke onset. Along with the added benefits of having tenecteplase on formulary come challenges of managing multiple thrombolytics for the same indication. Identifying key stakeholders and creating an interdisciplinary team are critical to ensure safe transitions. Institutions can safely transition from alteplase to tenecteplase as a thrombolytic of choice for AIS.

Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations.

Several research articles have been published within the last decade comparing the use of tenecteplase to alteplase in ischemic stroke management. Prior reporting on the comparative therapeutic efficacy and safety profiles of tenecteplase and alteplase is reviewed. Tenecteplase is a variant of native tissue-type plasminogen activator, which rapidly promotes thrombolysis by catalyzing formation of the serine protease plasmin. Tenecteplase has theoretical advantages over alteplase as it has greater fibrin specificity and has a longer half-life than alteplase. This allows the administration of a single bolus over 5 to 10 seconds, as opposed to a bolus followed by a 1-hour infusion with alteplase. While currently approved by the Food and Drug Administration for the treatment of ST-segment elevation myocardial infarction, tenecteplase has also been studied in the treatment of acute ischemic stroke and has extensive data for this off-label indication. The most comprehensive trials to date evaluating the use of tenecteplase in acute ischemic stroke include the TNK-S2B, Australian TNK, ATTEST, Nor-Test, and EXTEND-IA TNK trials. Findings from these randomized controlled studies suggest that tenecteplase is at least as efficacious as alteplase in terms of neurological outcomes. The majority of these studies also reported a trend toward improved safety profiles with the use of tenecteplase. Current clinical evidence shows that tenecteplase is not inferior to alteplase for the treatment of ischemic stroke and suggests that tenecteplase may have a superior safety profile. Furthermore, tenecteplase also has practical advantages in terms of its administration. This can potentially lead to a decrease in medication errors and improvement in door to thrombolytic time.

Tenecteplase Improves Door‐to‐Needle Time in Real‐World Acute Stroke Treatment

Background We report the interim results of a process improvement initiative at a comprehensive stroke center in which all tPA (tissue‐type plasminogen activator)–eligible patients were given tenecteplase for acute ischemic stroke. Methods We retrospectively analyzed a prospectively maintained single‐center registry of consecutive patients with acute ischemic stroke treated at our comprehensive stroke center emergency department or transferred for further care. Patients treated with alteplase (tPA) before the process improvement initiative (October 2019–April 2020) were compared with those treated with tenecteplase (May 2020–July 2021). The primary efficacy outcome was the Target: Stroke Phase II recommendation of door‐to‐needle (DTN) time ≤45 minutes. Backward stepwise logistic regression was used to estimate an independent effect of tenecteplase against DTN time ≤45 minutes. Two contemporaneous, negative controls (time to first emergency department antibiotic for patients who presented with infectious symptoms and door‐to‐groin puncture for thrombectomy) were evaluated to confirm DTN time was unrelated to emergency department and other stroke treatment throughput. Results Of the 113 included patients, 53 (47%) received tenecteplase. DTN time was significantly faster in patients treated with tenecteplase (median, 41 [interquartile range, 34–62] minutes versus 58 [interquartile range, 45–70] minutes; P &lt;0.01), with no significant difference in symptomatic intracranial hemorrhage (2% versus 7%; P =0.37). Despite the higher proportion of tPA patients being transferred for care (with slower DTN time), tenecteplase remained independently predictive of DTN time ≤45 minutes (adjusted odds ratio, 3.96; 95% CI, 1.58–9.91). There was no difference in time to first emergency department antibiotic ( P &gt;0.05) or door‐to‐puncture ( P &gt;0.05) when similar periods were compared. Conclusions Tenecteplase was associated with faster DTN time when compared with tPA in those with acute ischemic stroke. This can likely be attributed to the ease of single bolus administration of tenecteplase.

Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?

Should Tenecteplase be Given in Clinical Practice for Acute Ischemic Stroke Thrombolysis?

Thrombolysis with novel tenecteplase in acute ischemic stroke: A prospective observational study from a rural tertiary care center in South India

Tenecteplase is an approved engineered recombinant tissue plasminogen activator for treatment of acute ischemic stroke with molecular and practical advantages. It could be quintessential in this era of endovascular care provided that more studies come out, especially from resource poor settings. To observe the clinico-epidemiological profile and to assess the outcome of acute ischemic stroke patients treated with tenecteplase. A prospective observational study of stroke patients treated with tenecteplase. On admission clinical characteristics, temporal, epidemiological, imaging parameters, outcome measures including baseline NIHSS, NIHSS at 1 hour, 24 hours, at discharge, and modified Rankin Scores (mRS) at 0, 1 and 3 months were recorded in a structured proforma. Out of the 19 patients thrombolysed with tenecteplase 68.4% were males. Mean age of the study population was 61.3 years. Hypertension (57.9%), diabetes mellitus (36.8%) and smoking(26.3%) were the most common risk factors.Time parameters like mean onset to door time, door to image and door to needle time were 126 minutes, 29minutes and 66 minutes respectively, which were confirming with the international standards. Mean NIHSS was 11.1 and serial improvement was noted in the post treatment mean NIHSS scores at 1 hours, 24 hours and 7days with values of 8.6,8.0 and 7.7 respectively ( F=5.619,p=0.018). The mean mRS score was 3.5 and the follow up mRS at 1 month (2.4) and 3 months (1.7) (F=19.32, p&amp;#60;0.001) revealed significant functional improvement. The spearman test showed a positive correlation of age with all the serial post treatment NIHSS and mRS scores even when it did not affect the baseline NIHSS and mRS scores suggesting a poor response to tenecteplase with increasing age. Major improvement in mRS scores described as either a score of 0 or 1 or else a three-point improvement from baseline was seen in 47% (9) of thrombolysed patients and a major improvement in NIHSS scores was seen in 26% (5) patients. Symptomatic intracranial hemorrhage (sICH) was seen in only 5% of the study population. Thrombolysis with tenecteplase is faster, safer and effective but the treatment response decreases with increasing age.