TNK Group Research Articles

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.

Abstract WP24: Safety of Tenecteplase vs Alteplase in Telestroke: A Large Multistate Experience (STAT)

Background: Prompt treatment with IV thrombolytics (IVT) in acute ischemic stroke (AIS) patients is critical for improved recovery and survival. Recently, hospital systems are switching to the IVT tenecteplase (TNK) instead of the FDA approved alteplase (tPA) for treatment. Multiple studies and meta-analyses evaluating the efficacy and safety of TNK demonstrate similar or superior outcomes when compared to tPA. TNK is not FDA approved for treatment leading to hesitation and attention on the complications profile including intracranial hemorrhage (ICH) rates. Methods: AIS consults seen in the ED by TeleSpecialists, LLC at 220 facilities (26 states) from January 1, 2022 to May 31, 2023 were extracted from the TeleCare by TeleSpecialists TM database. The encounters were reviewed for IVT candidate, door to needle (DTN) time, IVT used, advanced imaging, LVO, complication occurrence, complication type, symptomatic ICH, and ECASS II ICH score. Comparison of complications was performed between the two groups by IVT: TNK or tPA. Comparison of continuous variables was performed by student’s t-test for normally distributed data, and the Mann-Whitney test for nonnormally distributed data. Pearson's Chi-square test was employed for comparisons of categorical variables. Results: A total of 2305 TNK patients and 3337 tPA patients were extracted. DTN times were faster (37 min vs 42 min, p < 0.0001) and more total complications were seen in the TNK group (87 vs 80, p =0.0035). In nonLVO IVT patients, TNK group had more complications (57 vs 47, p 0.0078), specifically ICH (48 vs 35, p= 0.0036). In LVO IVT patients, TNK group did not have a statistically significant difference in ICH (21 vs 18, p =0.07). In IVT patients not accepted for NIR, TNK group had more complications (77 vs 69, p=0.005), specifically ICH (63 vs 51, p=0.0026). In IVT patients accepted for NIR, no significant differences were observed. There were no statistically significant differences in symptomatic ICH between groups. Conclusions: TNK group was found to have significantly more complications including ICH compared to tPA group driven by non-LVO patients. Closer analysis of potential for increased risk to non-LOV patients is warranted based on this data from the largest simultaneously collected data.

Abstract WP31: Real World Comparison of Outcomes of IV Tenecteplase versus IV Alteplase for Acute Ischemic Stroke

Background: Tenecteplase (TNK) has been reported to be non-inferior to alteplase from a clinical outcome and safety standpoint according to recent studies. In our study, we compare the outcomes of IV TNK & IV alteplase for acute ischemic stroke patients. Materials and Methods: We evaluated acute AIS patients treated with IVT between10/2020-03/2023 at theDepartment of Neurology, Hackensack MeridianHealth, JFKMedical Center. All analyses was done using SPSS version 29 software. Results: Among the total 270 patients, 150(55.6%) received IV alteplase and 120(44.4%) received IV TNK. Major neurological improvement (defined as improvement in NIHSS score by 8 or more points at 24hours) was observed with TNK. Any intracranial hemorrhage was higher among patients treated with IV TNK compared to alteplase (25% versus 14.7%, p=0.024). Symptomatic intracranial hemorrhage(sICH) was higher inTNK group (8.3% versus3.3%, p=0.075). The proportion of routine discharge was higher among alteplase patients, while non-routine discharge was higher among TNK patients (51.7% vs. 28%, p<0.001). In the logistic regression analysis, patients treated with IV TNK were at a significantly higher risk of any intracranial hemorrhage(odds ratio[OR], 1.93, 95% confidence interval [CI]1.051-3.57, p=0.034). After adjusting for age, gender, NIHSS, thrombectomy, hypertension, diabetes, hyperlipidemia, CHF, previous TIA and previous stroke, there was anon-significant higher rate of intracranial hemorrhage. A nonsignificant decrease in the odds of symptomatic intracranial hemorrhage (sICH) was seen with TNK. There were significantly higher rates of non-routine discharge (OR, 3.078, 95% CI 1.8-5.19, p<0.001) and death (OR, 4.84, 95% CI1.20-19.66, p=0.002) inpatients treated with IV TNK. After adjusting for the above-mentioned factors, there was a significantly higher rate of non-routine discharge in the TNK group and a higher trend of death in the TNK group. Conclusions: We found that IV TNK was associated with higher rates of intracranial hemorrhage compared to IV alteplase in patients with acute ischemic stroke.

Abstract WMP8: Tenecteplase vs Alteplase: is Pro-Inflammatory and Procoagulant Response Any Different in Acute Ischemic Stroke?

Introduction: Thrombolysis in acute ischemic stroke (AIS) using Tenecteplase (TNK) is gaining popularity compared to Alteplase (ALT) for its practical advantages. At our center, we observed an improvement in clinical outcome in TNK treated patients compared to ALT. Hence, we aimed to study the pro-inflammatory and procoagulant responses post-thrombolysis and their contributory role in clinical outcome. Methods: This is a single-center retrospective study of ALT or TNK treated AIS patients admitted to a comprehensive stroke center over a 3-year period. Non-parametric tests were used to compare differences between the ALT and TNK cohorts. Peripheral blood indices, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and mean platelet volume to platelet count ratio (MPV:PLT), were calculated. Their rise from pre-thrombolysis baseline during the first 48 hours was used to define a systemic inflammatory and procoagulant response. A p-value of <0.05 was considered statistically significant. Results: During the study period, 165 and 64 patients were treated with ALT and TNK respectively. The baseline demographics, vascular risk factors, and admission stroke severity were similar. Admission NLR, PLR, MLR, and MPV:PLT were not statistically different. Clinical outcome at 3 months assessed using median modified Rankin Scale (mRS) was better with TNK (2.0 [IQR, 1.0, 4.0] vs 3.0 [IQR, 2.0, 5.0]; p = 0.0007). Rise in NLR was significantly higher in the ALT cohort compared to TNK on day 1 (2.25 [IQR, 0.0, 5.77] vs. 0.49 [IQR, -0.48, 3.91], p = 0.01) and day 2 (1.58 [IQR, -0.09, 5.68] vs. 0.39 [IQR, -0.96, 2.91], p = 0.045). Similarly, MLR on day 2 in the ALT cohort (0.16 [IQR, 0.05, 0.49] vs. 0.12 [IQR, -0.05, 0.22], p = 0.038) and MPV:PLT on day 1 (0.61 [IQR, 0.16, 1.35] vs. 0.32 [IQR, 0.003, 0.68], p = 0.002) and day 2 (0.83 [IQR, -0.35, 1.90] vs. 0.36 [IQR, -0.12, 1.21], p = 0.004) were higher. Conclusions: Patients treated with TNK had better mRS scores compared to ALT in our study. This was associated with significantly less inflammatory and procoagulant response during the first 48 hours of AIS in the TNK group. The etiology for such an association is speculative and needs confirmation using more specific biomarkers.

Abstract WP1: Analyzing Door-to-Needle Time Trends: Tenecteplase vs. Alteplase in Acute Ischemic Stroke Treatment

Introduction: Tenecteplase (TNK) presents potential advantages in the treatment of acute ischemic stroke (AIS) and is hypothesized to reduce door-to-needle times (DTN). Methods: The Lone Star Stroke (LSS) registry incorporates data from 9 (6 CSC, 3 PSC) Texas hospitals which have and have not switched to TNK, mapping subject data to Get-With-the-Guidelines (GWTG) stroke variables and including patients who received alteplase (ALT) or TNK from October 2019 to March 2023. The dataset is stratified into ALT and TNK groups, generating a univariate table for each measured variable which is further analyzed by descriptive statistics. Polynomial regression models for both ALT and TNK are constructed to explore trends in DTN. Results: Of 621 patients, 459 received ALT and 162 received TNK. The groups had similar mean ages [66.8 (14.4) vs 69.2 (14.7); P=.074], and similar NIHSS scores [11.1 (8.1) vs 11.1 (7.5); P>.977]. The median DTN for ALT of 44 (32-61) mins was similar to 43 (32-61) mins for TNK (P>.05). The proportion of patients meeting DTN cut points was similar, comparing ALT to TNK for <60 minutes (73.9% vs 74.5%); for <45 minutes (50.3% vs 54.3%); and <30 minutes (20.7% vs 21.0%). As shown in Figure 1, regression models indicate no significant temporal trends for ALT (r 2 =.006; P=.08) nor for TNK (r 2 =.015; P=.12). Conclusion: Both TNK and ALT displayed comparable DTN times and exhibited similar temporal trends. Given the timeframe of our cohort, these decreasing trends in DTN times may be influenced by relaxed COVID restrictions and reduced workflow delays. The transition to TNK does not appear to impact workflow nor does it appear to impact stroke core measures. This is likely due to similar inclusion and exclusion criteria, as well as similar administration processes for both medications. The results are encouraging for hospitals seeking to transition to TNK in that these hospitals are unlikely to experience a change in DTN or other stroke core measures during the transition period.

Abstract WP26: Effectiveness of Tenecteplase versus Alteplase in Acute Ischemic Stroke Selected Subgroups of a Real-World-Data Set

Introduction: Tenecteplase is increasingly utilized as an alternative acute ischemic stroke (AIS) thrombolytic to Alteplase (tPA). Although many larger AIS trials have demonstrated the non-inferiority of TNK, Real World Data in many specific subgroups continue to be lacking. We studied the comparative effectiveness of AIS thrombolysis with TNK to tPA at our institution, focusing on currently understudied cohorts. Methods: We conducted a retrospective cohort analysis of AIS patients treated with thrombolysis within our health system. We utilized the Get With the Guidelines (GWTG) database to obtain basic demographic data. Additional variables and key outcomes (functional and radiographic) were abstracted independently by two authors from the electronic record. Disagreements were resolved by mutual consensus or a third investigator. An ordinal logistic regression model was used to assess the interventions' effectiveness, with the outcome being the modified Rankin Scale (mRS) score 90 days post-stroke. Subgroups included Age (<60, 61-80, >80), location of vessel occlusion (Large or Medium vessel), thrombolysis in the extended time window (beyond 4.5 hours), treatment via telestroke, and thrombectomy. Results: There were 500 consecutive AIS patients with complete outcome data. The mean age of the participants was 70.1 years, with 52.7% of patients being male. In the adjusted ordinal logistic regression analysis, the TNK group presented with 1.00 odds of a worse mRS score than the tPA group (95% CI 0.57-1.74). Subgroup regression analysis demonstrated no heterogeneity in effect size. Figure 1 is a Forest Plot demonstrating the Odds Ratio for each subgroup. Conclusions: It’s well-published that TNK is a comparable treatment for AIS and has demonstrated advantages. This analysis compared specific subgroups of real-world patients and showed no heterogeneity. This real-world subgroup analysis adds to the literature supporting the use of TNK for the treatment of AIS.

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<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>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>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.

Tenecteplase Plus Butyphthalide for Stroke Within 4.5-6 Hours of Onset (EXIT-BT): a Phase 2 Study.

To date, the benefit of intravenous thrombolysis is confined to within 4.5h of onset for acute ischemic stroke (AIS) without advanced neuroimaging selection. The current trial aimed to investigate the safety and efficacy of intravenous tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6h of onset. In this randomized, multicenter trial, eligible AIS patients were randomly assigned to receive intravenous TNK (0.25mg/kg) plus NBP or NBP within 4.5 to 6h of onset. The primary endpoint was symptomatic intracranial hemorrhage (sICH). Secondary endpoints included excellent functional outcome defined as a modified Rankin Scale score of 0 to 1 at 90days. 100 patients diagnosed by non-contrast CT (NCCT) were enrolled, including 50 in TNK group and 50 in control group. sICH occurred in 2.0% (1/50) in TNK group and 0.0% (0/49) in control group with no difference (unadjusted P = 0.998). The proportion of excellent functional outcome was 77.6% (38/49) in TNK group and 69.4% (34/49) in control group with non-significance (absolute difference 8.2%, P = 0.36). A significant decrease in NIHSS score at 24h (P = 0.004) and more early neurological improvement (20.4% vs 4.1%; P = 0.026) was observed in TNK vs control group, but there was no difference in other secondary outcomes. This phase 2 study suggests that intravenous TNK with adjuvant NBP seems safe, feasible and may improve early neurological function in AIS patients within 4.5 to 6h of symptom onset selected using NCCT.Clinical Trials Registration: This trial was registered with ClinicalTrials.gov (NCT05189509).

Efficacy and Safety of Streptokinase and Tenecteplase in Patients with ST Elevation Myocardial Infarction

Objective: To investigate the efficacy and safety of Streptokinase (STK) and Tenecteplase (TNK) in ST elevation myocardial infarction patients. Study Design: Randomized control trial. Place and duration: Study was conducted at Ch Pervaiz Ellahi institute of cardiology hospital Multan from May 2022 to April 2023. Methodology: Patients of ST elevation myocardial infarction presented within six hours of onset of symptoms were included in the study. Patients were divided into two equal groups (STK and TNK). Patients in STK group were thrombolysed with streptokinase and in TNK group were treated with Tenecteplase. SPSS version 23 was used for data analysis. Results: ST-resolution Pre-PCI at 90 minutes in STK and TNK groups was observed as 68% and 80%, respectively. While post-PCI ST-resolution was found in 80% and 88% patients of STK and TNK groups, respectively. Major bleeding events were found in 8% patients of STK Group and in 4% patients of TNK Group. The differences were statistically insignificant, and no association was found. Conclusion: Both drugs Streptokinase and Tenecteplase are equally effective when given in correct timeline in patients of ST segment myocardial infarction. Efficacy and safety of TNK is also like STK when administered in equal time frame.

Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Systematic Review and Meta-analysis.

A number of clinical trials have compared tenecteplase (TNK) and alteplase for the management of acute ischemic stroke (AIS) and the results are inconsistent. Present systematic review and meta-analysis is undertaken to analyse the efficacy and safety of TNK in AIS compared to alteplase. A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, for a period from inception to September 2022, with the keywords i.e., "tenecteplase" and "alteplase" and "acute ischemic stroke." Clinical trials published in English that compared the efficacy and safety of TNK to alteplase in AIS were included. The major outcomes of this meta-analysis were proportion of patients free from disability and functional independence at 90 days, early neurological improvement at 24 hours, all-cause mortality at 90 days, patients with intra cranial hemorrhage (ICH), and patients with severe disability at 90 days. A total of nine studies with 3,573 patients were included in the analysis. The proportion of patients with freedom from disability was comparable in both groups (relative risk [RR] = 1.04, 95 per cent CI = 0.92-1.17; p = .53). Similarly, proportion of patients with functional independence was comparable (RR = 1.12, 95 per cent CI = 0.96-1.31; p = .14). TNK group had a higher rate of early neurological recovery (RR = 1.56, 95 per cent CI = 0.96-2.54; p = .07). All-cause mortality at 90 days was comparable in both groups (RR = 0.97; 95 per cent CI = 0.72-1.29; p = .82). The proportion of patients with ICH was higher in TNK group (RR = 1.14, 95 per cent CI = 0.77-1.68; p = .52). The proportion of patients with severe disability was less in TNK group (RR =0.84, 95 per cent CI = 0.53-1.32; p = .44). TNK was similar to alteplase in terms of efficacy and safety. The patients in TNK group showed early neurological improvement but were simultaneously at higher risk of ICH. The TNK can be an alternative to alteplase if the benefits outweigh the risks.

Abstract 069: Alteplase Or Tenecteplase Prior To Endovascular Therapy – Does It Matter?

Introduction Thrombolysis with recombinant tissue plasminogen activator remains vital to acute ischemic stroke (AIS) therapy. Several centers in the United States are adopting Tenecteplase (TNK) over Alteplase (ALT) due to its ease of administration, fibrin specificity, longer half‐life, and non‐inferiority of TNK compared to ALT [1‐2]. In this study, we investigated whether there is any difference in clinical outcomes among patients undergoing endovascular therapy (EVT) pretreated with ALT vs. TNK. Methods This is a single‐center retrospective study of patients presenting with AIS between January 1, 2020 and December 31, 2022, and treated with either ALT or TNK that subsequently underwent EVT. Non‐parametric tests were used to compare differences between ALT and TNK groups. A p‐value of <0.05 was considered statistically significant. Effect size is reported using Hedges’ G statistic, and the sample size is calculated to estimate the study cohort needed for a randomized controlled trial using real‐world practice data. Results During the study period, 165 patients were treated with ALT, and 64 patients were treated with TNK. There was no difference between the ALT and TNK cohorts in their baseline demographic characteristics or premorbid vascular risk factors. Of the 165 patients undergoing thrombolysis, 75 also underwent EVT, with 55 patients treated with ALT compared to 20 patients treated with TNK. The admission National Institutes of Health Stroke Scale scores (NIHSS) were similar. Although the time of symptom onset to thrombolysis was faster in the TNK group, it was not statistically different from the ALT group. Time to EVT from symptom onset was faster in the TNK group (median time 391.0 vs. 190.0 min, p=0.00021). However, discharge NIHSS was not statistically different (mild [18 (34.0%) vs. 9 (47.4%)], moderate [10 (18.0%) vs. 1 (5.3%)], moderate to severe [13 (24.5%) vs. 4 (21.1%)], severe [12 (22.6%) vs. 5 (26.3%)], p=0.472). Using NIHSS (16 and above) as the outcome of interest – it is noted that the number needed to treat (NNT) in this subgroup was ‐27. This implies that when TNK is used as a thrombolytic therapy before EVT, it will result in one additional adverse event (NIHSS of 16 and above) compared to ALT. Comparing ALT and TNK patients undergoing EVT according to their 3‐month mRS, an effect size of 0.274 is noted using Hedges’ G, indicative of a small to moderate effect size. It would require 478 patients (with 239 in each group) to detect a difference that the randomness in our current cohort may otherwise mask. Conclusion Despite several practical advantages and faster treatment with TNK, our study failed to provide evidence of its superiority compared to ALT in patients undergoing EVT. Furthermore, we noted a potential harm among TNK‐treated patients compared to ALT. This observation needs further investigation to determine if certain local and systemic factors might contribute to TNK’s adverse outcome profile in the EVT population despite its pharmacological superiority compared to ALT.

Abstract 040: Hemorrhagic Conversion Patterns After Transition of Stroke Thrombolysis from Alteplase to Tenecteplase; Real‐World Experience

Introduction Importance:Tenecteplase (TNK) use is more prevalent as the thrombolytic drug of choice for acute ischemic stroke (AIS), given its ease of use with results from randomized trials showing non‐ inferiority and comparable safety to Alteplase (tPA). However, there is conflicting data in terms of intracranial hemorrhage risk. Objective: We are reporting the rate of symptomatic intracranial hemorrhage(sICH) in TNK and tPA treated stroke populations across two large hospital systems. Methods Design: Retrospective cohort observational study. Data was collected from April 1, 2022 through March 29, 2023. Setting: Data was collected from 15 stroke centers: 10 primary and 5 comprehensive stroke centers in Texas. Participants: Inclusion criteria: 18 years or older, suspected to have an AIS were eligible to receive thrombolytic therapy, and received either IV TNK or tPA at the standard dose. A total of 431 patients were included. 216 patients received alteplase and 215 patients received tenecteplase. Exposure: Data was collected 90 days before and 90 days after the stroke center changed from tPA to TNK. Main Outcomes: The primary endpoint was to compare the incidence of sICH according to SITS‐MOST/ECASS‐3 criteria in the tPA and TNK groups. Secondary endpoints included the radiographic pattern of hemorrhagic conversion according to the Heidelberg bleeding classification (HBc). Results A total of 431 patients; half of them had been administered Alteplase (n=216) and the other half had Tenecteplase (n=215). Approximately half of them were females 110 (51%) for alteplase and 117 (54%) for Tenecteplase. Almost 2/3 of the study population never smoked; 66% for alteplase 64% for Tenecteplase. Majority of the patient population got thrombolytic therapy within 3 hours 174 (81%) for alteplase versus 176 (82%) for Tenecteplase. 34 patients (15%) in the alteplase group as compared to 26 patients (12%) in the Tenecteplase group had endovascular thrombectomy attempted. 7 patients in the tPA group (3.2%) and 14 patients (6.5%) in the TNK group had sICH. An increase in the NIHSS on arrival (p=0.048) was a statistically significant predictor of sICH. A two sample proportion test on TNK produced a statistically significant increase in Heidelberg Bleed class 3 (HBc3) (p=0.040) over tPA. Conclusion We observed increased cases of bleeding associated with TNK administration with statistically significant increase in the HBc3 when compared to patients who received tPA. Suggested mechanisms of bleeding are hemorrhagic conversion in clinically silent infarcts, and contusions underlying the lesions. These findings suggest a potential need to reevaluate the criteria for administering TNK to patients. Larger studies are required to confirm this data.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5-24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study.

Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5-24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0-1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46-2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0-2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5-24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Efficacy of intravenous thrombolysis with tenecteplase in treating the branch atheromatous disease

Objective: To explore the efficacy of intravenous thrombolysis with tenecteplase (TNK) in the treatment of branch atheromatous disease (BAD). Methods: A total of 148 BAD patients hospitalized in the stroke center of Zhengzhou People's Hospital from January 2020 to March 2023 were retrospectively included. According to whether TNK was used for treatment, the patients were divided into the TNK group (52 cases) and the control group (96 cases). The propensity score matching (PSM) method was used to eliminate baseline differences between the two groups, and 46 pairs were successfully matched. Early neurological deterioration (END) was defined as an increase in the national Institutes of Health Stroke Scale (NIHSS) scores within 7 days of stroke≥2. The 90-day modified Rankin Scale (mRS) was used to compare the long-term efficacy between the two groups. A binary logistic regression model was used to analyze the influencing factors of clinical outcomes in patients with BAD. Results: Among the 92 patients, 62 were males and 30 were females, with an average age of (61.0±9.5) years. After PSM, there were statistically significant differences in NIHSS score at discharge [2 (0, 4) vs 4 (3, 8)] and length of hospital stay [9 (6, 13) d vs 11 (9, 14) d] (both P<0.05) between the two groups. The proportion of mRS 0-2 in TNK group was higher than that in the control group [82.6%(38/46) vs 60.8%(28/46)], while the proportion of END and mRS≥4 was lower than that in the control group [10.8%(5/46) vs 30.4%(14/46); 8.7%(4/46) vs 26.0%(12/46)], with statistically significant differences (P<0.05). The 90-day mortality in the control group was 2.2% (1/46), while no death was detected in the TNK group. Conclusion: Intravenous thrombolysis therapy with TNK can not only increase the proportion of 90-day mRS 0-2 in BAD patients, but also reduce the incidence of END.

Thrombolysis in STEMI in the era of COVID – Holding fort in cardiologist deficit locales

During the COVID-19 pandemic, the pharmaco-invasive approach in the management of ST Elevation Myocardial Infarction (STEMI) played a vital role in saving many lives. A retrospective observational study was conducted wherein 134 patients presenting with STEMI between (Dec 2019–Mar 2022) were thrombolysed with either streptokinase or tenecteplase in a centre where primary PCI was not available. There was no significant difference in the outcomes and their predictors between the SK and TNK groups. A prospective study with a larger sample size in the Indian population will be able to provide more substantial and promising results for further interventions.

The efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis.

We aimed to evaluate the available evidence on the efficacy and safety outcomes of intravenous tenecteplase (TNK) compared with intravenous alteplase(ALT) for patients with acute ischemic stroke (AIS) in randomized controlled trials (RCTs). The MEDLINE/PubMed, Embase, Springer, Web of Science, Cochrane Collaboration database, China National Knowledge Infrastructure (CNKI) database, and Wanfang database were comprehensively searched for RCTs regarding the effects of TNK versus ALT among AIS patients in these English and Chinese electronic databases from inception dates to August 1, 2022. This meta-analysis followed PRISMA guidelines. Two reviewers independently retrieved RCTs and extracted relevant information. The methodological quality of the included trials was estimated using the Cochrane risk of bias tool. The pooled analyses were performed using RevMan 5.3 software. The primary outcome was functional outcome on the modified Rankin Scale (mRS) (range 0 to 5) and mortality at 90days. The secondary outcomes included successful recanalization, early neurologic improvement < 48h, any intracranial hemorrhage (ICH), and symptomatic ICH. The follow-up time of all studies was at least 3months. A total of nine RCTs involving 1958 patients in TNK group and 1731 patients in ALT group were finally included. For the efficacy outcomes, there were no significant differences between the two groups in terms of mRS score 0 ~ 2 (RR 1.00; 95% CI 0.88-1.13; P = 0.96), mRS score 0 ~ 1 (RR 1.03; 95% CI 0.96-1.10; P = 0.36), successful recanalization (RR 1.25; 95% CI 0.88-1.76; P = 0.21), and early neurologic improvement < 48h (RR 1.08; 95% CI 0.92-1.26; P = 0.37). Similar results were seen for the safety outcomes, which have no statistical differences in terms of any ICH (RR 1.01; 95% CI 0.72-1.41; P = 0.96), symptomatic ICH (RR 1.19; 95% CI 0.81-1.76; P = 0.37), and mortality at 90days (RR 0.99; 95% CI 0.83-1.19; P = 0.94). Overall, the efficacy and safety outcomes of intravenous thrombolysis with TNK versus ALT for AIS were not statistically different. However, TNK at a dose of 0.25mg/kg may be a reasonable alternative to ALT for thrombolysis.

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.

Abstract TP4: Freezing Tenecteplase Aliquots Reduces Waste And Achieves Similar Door To Needle Times And Reperfusion Rates

Objective: To determine the feasibility of using previously frozen tenecteplase (TNK) to treat acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Methods: This is a single-center proof of concept prospective study that was retrospectively analyzed. We began using freshly reconstituted TNK to treat AIS due to LVO in May 2020. In March 2022 we began dividing the 50mg vial of TNK into two frozen 25mg aliquots based on a previously published stability and bioactivity study comparing thawed TNK to freshly reconstituted samples. Our primary outcome was door-to-needle time (DTN) which was analyzed with a quantile regression specifying the median, which was adjusted for age, NIHSS and delays related to treating hypertension. Binomial logistic regression analyses were used to assess secondary outcomes of TNK recanalization rate prior to mechanical stroke thrombectomy (MST) and excellent reperfusion scores (≥TICI 2C) after MST in the fresh and previously frozen TNK groups. Results: Five frozen TNK vials (ten aliquots) had been created since implementation of freezing TNK. Seven previously frozen aliquots were thawed and used, while three aliquots expired and were discarded. We analyzed the seven previously frozen TNK aliquots against the sixty eight freshly reconstituted TNK vials used to treat acute ischemic stroke patients. Median DTN was similar between previously frozen, 41 (IQR, 27 - 53) and fresh TNK, 46 (IQR, 37 - 60), p = 0.12. There was no difference in the LVO recanalization rate prior to MST in previously frozen, 0 (0.0%) and fresh TNK, 2 (2.9%), p = 0.99. Patients undergoing MST achieved similar rates of excellent reperfusion in previously frozen, 4 (66.7%) and fresh, 30 (56.6%) TNK treated patients, Odds Ratio = 1.55 [95%CI, 0.25, 9.70], p = 0.64 Conclusions: It is feasible to freeze 50mg vials of TNK into two 25mg aliquots to use to treat acute ischemic stroke. We found similar DTN times, indicating that thawing the previously frozen TNK did not delay IV thrombolysis administration. Additionally, we found similar reperfusion rates prior to and after MST with freshly reconstituted and previously frozen TNK.

Biosimilar Tenecteplase Versus Alteplase in Acute Ischemic Stroke: A Real World Study.

There is an unmet need for a more effective thrombolytic agent in acute ischemic stroke (AIS) management. Various studies and meta-analysis suggest tenecteplase (TNK) as non-inferior over alteplase (rTPA). The present single-center study compares biosimilar TNK and rTPA in a tertiary care setting. Data of patients who presented with AIS and underwent intravenous thrombolysis (IVT) were recruited retrospectively from January 2018 to July 2021. Primary efficacy outcome was a modified Rankin score (mRS) at 90 days dichotomized at < = 2. Qualitative and quantitative variables were assessed using Chi-square test and Student's t-test, respectively. A total of 160 patients, 103 in the rTPA and 57 in TNK group, were analyzed. The baseline characteristics were well matched apart from hypertension. Large artery atherosclerosis was the most frequent subtype of stroke among the two groups. Good functional outcome was seen in 47.92% of patients TNK and 64.77% of patients in rTPA group (p = 0.069). No difference was seen in the rates of any ICH (p = 0.29) and mortality at 3 months (p = 0.32) among the two groups. This present study observed no difference in the efficacy and safety between biosimilar TNK and rTPA. Our findings are in concordance with published trials showing equivalence between the two molecules.

Efficacy Outcomes of Tenecteplase versus Alteplase in Patients with Ischemic Stroke in Therapeutic Window: Experience from a Single Institution

Background and Aim: The World Health Organization estimated that 15 million people throughout the world suffer stroke every year. Only 5%–10% of all acute ischemic stroke (AIS) patients presenting to emergency departments (EDs) are eligible for and receive thrombolytic therapy. This study was conducted to assess and compare the efficacy and safety profile of thrombolysis with tenecteplase (TNK) with that of alteplase among patients with AIS who were eligible for thrombolysis. Materials and Methods: This was a hospital-based prospective observational study. All the patients who presented with AIS within the time window period of ≤4.5 h to ED of Sher-i-Kashmir Institute of Medical Sciences, Soura, from September 2018 to March 2021, were screened for eligibility of thrombolysis by TNK. A total of 76 patients were enrolled; among which 42 were thrombolysed with TNK and 34 patients were thrombolysed with alteplase. These data were compared with departmental data of patients thrombolysed by alteplase during July 2015–July 2017. Inclusion and exclusion criteria used in the study were as per the American Heart Association/American Stroke Association guidelines for thrombolysis. Efficacy and safety were assessed and compared of the two drugs. Results: After 24 h of thrombolysis, early neurological improvement occurred in 62% of TNK patients compared to only 35% of patients from alteplase group, which was significant statistically (P &lt; 0.05). An excellent functional outcome, defined as the Modified Rankin Scale (mRS) of 0–1 at 3 months of discharge, was seen in 67.6% of TNK and 48.5% of alteplase group. A poor recovery, defined as the mRS of 4–6 at 3 months of follow-up, was seen in 16% and 21% in TNK and alteplase group patients, respectively. Conclusion: TNK appears to be characterized by a better safety and efficacy profile than alteplase; however, further multicenter studies and randomized controlled trials are required to confirm our preliminary findings.