Early Experience With Tenecteplase at a Comprehensive Stroke Center.
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ABSTRACT: Purpose of review
Tenecteplase has been studied and recommended as an alternative thrombolytic agent in patients with acute stroke. A brief review of clinical trials and guidelines pertinent to our clinical decision algorithm is described. This is followed by operational steps that were made to create and implement a clinical pathway based on available evidence in which tenecteplase is used in select patients with stroke at our comprehensive stroke center.Recent findings
A number of patients have been treated at our center with IV tenecteplase. A case is presented to illustrate the successful implementation of this new process.Summary
Development of our protocol is discussed in detail to enable other centers to create their own clinical pathways for thrombolytic treatment of acute ischemic stroke using tenecteplase.
SUBMITTER: Panezai S
PROVIDER: S-EPMC8723952 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Early Experience With Tenecteplase at a Comprehensive Stroke Center.
Panezai Spozhmy S Dubinsky Ilya I Sahito Sindhu S Gadallah Nancy N Suhan Laura L Mehta Siddhart S Kirmani Jawad J
Neurology. Clinical practice 20211201 6
<h4>Purpose of review</h4>Tenecteplase has been studied and recommended as an alternative thrombolytic agent in patients with acute stroke. A brief review of clinical trials and guidelines pertinent to our clinical decision algorithm is described. This is followed by operational steps that were made to create and implement a clinical pathway based on available evidence in which tenecteplase is used in select patients with stroke at our comprehensive stroke center.<h4>Recent findings</h4>A number ...[more]
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Project description:One in five ischaemic strokes affects the posterior circulation. Basilar artery occlusion is a type of posterior circulation stroke associated with a high risk of disability and mortality. Despite its proven efficacy in ischaemic stroke more generally, alteplase only achieves rapid reperfusion in ~4% of basilar artery occlusion patients. Tenecteplase is a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, which can be administered by intravenous bolus. The single-bolus administration of tenecteplase vs. an hour-long alteplase infusion is a major practical advantage, particularly in "drip and ship" patients with basilar artery occlusion who are being transported between hospitals. Other practical advantages include its reduced cost compared to alteplase. The EXTEND-IA TNK trial demonstrated that tenecteplase led to higher reperfusion rates prior to endovascular therapy (22 vs. 10%, non-inferiority p = 0.002, superiority p = 0.03) and improved functional outcomes (ordinal analysis of the modified Rankin Scale, common odds ratio 1.7, 95% CI 1.0-2.8, p = 0.04) compared with alteplase in large-vessel occlusion ischaemic strokes. We recently demonstrated in observational data that tenecteplase was associated with increased reperfusion rates compared to alteplase prior to endovascular therapy in basilar artery occlusion [26% (n = 5/19) of patients thrombolysed with TNK vs. 7% (n = 6/91) thrombolysed with alteplase (RR 4.0 95% CI 1.3-12; p = 0.02)]. Although randomized controlled trials are needed to confirm these results, tenecteplase can be considered as an alternative to alteplase in patients with basilar artery occlusion, particularly in "drip and ship" patients.
| S-EPMC8377762 | biostudies-literature
Project description:Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.
| S-EPMC7606819 | biostudies-literature
Project description:BACKGROUND:Alteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase. METHODS/DESIGN:NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial designed to establish superiority of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg (10% bolus?+?90% infusion/60 minutes) for consecutively admitted patients with acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a) admitted <4½?hours after symptoms onset; b) admitted <4½?hours after awakening with stroke symptoms c) receiving bridging therapy before embolectomy.Randomisation tenecteplase:alteplase is 1:1. The primary study endpoint is favourable functional outcome defined as modified Rankin Scale 0-1 at 90 days. Secondary study endpoints are: 1) haemorrhagic transformation (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24-48 hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24-36 hours; 5) death. DISCUSSION:NOR-TEST may establish a novel approach to acute ischaemic stroke treatment. A positive result will lead to a more effective, safer and easier treatment for all acute ischaemic stroke pasients.NOR-TEST is reviewed and approved by the Regional Committee for Medical and Health Research Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov (NCT01949948).
| S-EPMC4029902 | biostudies-literature
Project description:ImportanceEndovascular therapy (EVT) improves functional outcomes in acute ischemic stroke (AIS) with large vessel occlusion (LVO). Whether implementation of a regional prehospital transport policy for comprehensive stroke center triage increases use of EVT is uncertain.ObjectiveTo evaluate the association of a regional prehospital transport policy that directly triages patients with suspected LVO stroke to the nearest comprehensive stroke center with rates of EVT.Design, setting, and participantsThis retrospective, multicenter preimplementation-postimplementation study used an interrupted time series analysis to compare treatment rates before and after implementation in patients with AIS arriving at 15 primary stroke centers and 8 comprehensive stroke centers in Chicago, Illinois, via emergency medical services (EMS) transport from December 1, 2017, to May 31, 2019 (9 months before and after implementation in September 2018). Data were analyzed from December 1, 2017, to May 31, 2019.InterventionsPrehospital EMS transport policy to triage patients with suspected LVO stroke, using a 3-item stroke scale, to comprehensive stroke centers.Main outcomes and measuresRates of EVT before and after implementation among EMS-transported patients within 6 hours of AIS onset.ResultsAmong 7709 patients with stroke, 663 (mean [SD] age, 68.5 [14.9] years; 342 women [51.6%] and 321 men [48.4%]; and 348 Black individuals [52.5%]) with AIS arrived within 6 hours of stroke onset by EMS transport: 310 of 2603 (11.9%) in the preimplementation period and 353 of 2637 (13.4%) in the postimplementation period. The EVT rate increased overall among all patients with AIS (preimplementation, 4.9% [95% CI, 4.1%-5.8%]; postimplementation, 7.4% [95% CI, 7.5%-8.5%]; P < .001) and among EMS-transported patients with AIS within 6 hours of onset (preimplementation, 4.8% [95% CI, 3.0%-7.8%]; postimplementation, 13.6% [95% CI, 10.4%-17.6%]; P < .001). On interrupted time series analysis among EMS-transported patients, the level change within 1 month of implementation was 7.15% (P = .04) with no slope change before (0.16%; P = .71) or after (0.08%; P = .89), which indicates a step rather than gradual change. No change in time to thrombolysis or rate of thrombolysis was observed (step change, 1.42%; P = .82). There were no differences in EVT rates in patients not arriving by EMS in the 6- to 24-hour window or by interhospital transfer or walk-in, irrespective of time window.Conclusions and relevanceImplementation of a prehospital transport policy for comprehensive stroke center triage in Chicago was associated with a significant, rapid, and sustained increase in EVT rate for patients with AIS without deleterious associations with thrombolysis rates or times.
| S-EPMC8353578 | biostudies-literature
Project description:Purpose of reviewIntravenous thrombolysis is the first-line therapy for ischemic stroke, and alteplase has been used as an intravenous thrombolysis drug for over 20 years. However, considering its low rate of recanalization and risk of intracerebral hemorrhage, alteplase may not be the optimal thrombolytic drug of choice for ischemic stroke. Tenecteplase (TNK) is a genetically engineered, mutant, tissue plasminogen activator that is a potential substitute to alteplase in ischemic stroke. The pharmacokinetic advantages of TNK include greater fibrin selectivity than alteplase and prolonged half-life time. In this review, we have summarized the clinical trials of TNK in ischemic stroke.Recent findingsClinical trials showed a higher recanalization rate of TNK over alteplase without increasing the rate of intracerebral hemorrhage. However, not all clinical trials showed superiority of TNK over alteplase in functional outcomes and early neurological improvement. TNK was superior to alteplase in terms of recanalization in patients who fulfilled the imaging mismatch criteria and in those planning to undergo mechanical thrombectomy.SummaryTNK has the potential to substitute alteplase for ischemic stroke therapy. Future TNK clinical trials that target functional outcomes are warranted.
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Project description:BackgroundTimely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging penumbra. We re-evaluated the previously described PROTECT (PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy) Plus technique at a tertiary comprehensive stroke center.MethodsWe retrospectively analyzed all patients who underwent mechanical thrombectomy with stentrievers between May 2011 and April 2020. Patients were divided between those who underwent PROTECT Plus and those who did not (proximal balloon occlusion with stent retriever only). We compared the groups in terms of reperfusion, groin to reperfusion time, symptomatic intracranial hemorrhage (sICH), modified Rankin Scale (mRS) score at discharge.ResultsWithin the study period, 167 (71.4%) PROTECT Plus and 67 (28.6%) non-PROTECT patients which met our inclusion criteria. There was no statistically significant difference in the number of patients with successful reperfusion (mTICI >2b) between the techniques (85.0% vs 82.1%; p = 0.58). The PROTECT Plus group had lower rates of mRS ≤2 at discharge (40.1% vs 57.6%; p = 0.016). The rate of sICH was comparable (p = 0.35) between the PROTECT Plus group (7.2%) and the non-PROTECT group (3.0%).ConclusionThe PROTECT Plus technique using a BGC, a distal reperfusion catheter and stent retriever is feasible for recanalization of large vessel occlusions. Successful recanalization, first-pass recanalization and complication rates are similar between PROTECT Plus and non-PROTECT stent retriever techniques. This study adds to an existing body of literature detailing techniques that use both a stent retriever and a distal reperfusion catheter to maximize recanalization for patients with large vessel occlusions.
| S-EPMC10649534 | biostudies-literature
Project description:BackgroundTenecteplase has been approved for acute ischemic stroke at a dose of 0.2 mg/kg by the Indian licensing authority. A registry to evaluate the safety of tenecteplase was mandated by the licensing authority. The research aim was to use the Indian Registry in Ischemic Stroke-Tenecteplase (IRIS-TNK) to assess the safety and clinical outcomes in patients treated with tenecteplase in routine clinical practice.Methods and resultsIn this prospective, registry-based observational, cohort study, the primary outcome was proportion of symptomatic intracerebral hemorrhages at 36±6 hours after treatment. Secondary outcomes included improvement in National Institutes of Health Stroke Scale (NIHSS) score by either ≥4 or 8 points or an NIHSS score of 0, assessment of excellent outcome (modified Rankin Scale score 0 or 1), functional independence (modified Rankin Scale score 0-2), and Barthel Index score. From October 2017 to May 2023, 1015 patients with a median age of 62 years (interquartile range [IQR, 52-71 years]) were recruited across India. The median baseline NIHSS score was 9 (IQR, 6-13). The proportion of patients with symptomatic intracerebral hemorrhage was 0.6% (95% CI, 0.2-1.3%), and 10 patients (1% [95% CI, 0.5-1.9%]) died within 3 months. Improvement in NIHSS score by ≥4 points or an NIHSS score of 0 at 24 hours was observed in 34.4% (95% CI, 31.5-37.4%) of patients. An excellent outcome (modified Rankin Scale score 0 or 1) at 3 months was achieved in 55.4% (95% CI, 52.3-58.5%) of patients.ConclusionsThese results confirm that tenecteplase at a dose of 0.2 mg/kg is safe in routine clinical practice, when administered within 4.5 hours of symptom onset.Registrationhttps://ctri.nic.in/Clinicaltrials/. Identifier: CTRI/2017/11/010380.
| S-EPMC11681559 | biostudies-literature
Project description:BackgroundImmunotherapeutic early-phase clinical trials (ieCTs) increasingly adopt large expansion cohorts exploring novel agents across different tumor types. High-grade glioma (HGG) patients are usually excluded from these trials.MethodsData of patients with recurrent HGGs treated within multicohort ieCTs between February 2014 and August 2019 (experimental group, EG) at our Phase I Unit were retrospectively reviewed and compared to a matched control group (CG) of patients treated with standard therapies. We retrospectively evaluated clinical, laboratory, and molecular parameters through univariate and multivariate analysis. A prospective characterization of circulating leukocyte subpopulations was performed in the latest twenty patients enrolled in the EG, with a statistical significance cutoff of P < .1.ResultsThirty HGG patients were treated into six ieCTs. Fifteen patients received monotherapies (anti-PD-1, anti-CSF-1R, anti-TGFβ, anti-cereblon), fifteen patients combination regimens (anti-PD-L1 + anti-CD38, anti-PD-1 + anti-CSF-1R). In the EG, median progression-free survival and overall survival (OS) from treatment initiation were 1.8 and 8.6 months; twelve patients survived more than 12 months, and two of them more than 6 years. Univariate analysis identified O 6-methylguanine DNA methyltransferase (MGMT) promoter methylation and total protein value at six weeks as significantly correlated with a better outcome. Decreased circulating neutrophils and increased conventional dendritic cells levels lead to significantly better OS.ConclusionsA subgroup of EG patients achieved remarkably durable disease control. MGMT promoter methylation identifies patients who benefit more from immunotherapy. Monitoring dynamic changes of innate immune cell populations may help to predict clinical outcomes.
| S-EPMC8661084 | biostudies-literature
Project description:Background and purposeIn-hospital stroke-onset assessment and management present numerous challenges, especially in community hospitals. Comprehensive analysis of key stroke care metrics in community-based primary stroke centers is under-studied.MethodsMedical records were reviewed for patients admitted to a community hospital for non-cerebrovascular indications and for whom a stroke alert was activated between 2013 and 2019. Demographic, clinical, radiologic and laboratory information were collected for each incident stroke. Descriptive statistical analysis was employed. When applicable, Kruskal-Wallis and Chi-Square tests were used to compare median values and categorical data between pre-specified groups. Statistical significance was set at alpha = 0.05.ResultsThere were 192 patients with in-hospital stroke-alert activation; mean age (SD) was 71.0 years (15.0), 49.5% female. 51.6% (99/192) had in-hospital ischemic and hemorrhagic stroke. The most frequent mechanism of stroke was cardioembolism. Upon stroke activation, 45.8% had ischemic stroke while 40.1% had stroke mimics. Stroke team response time from activation was 26 minutes for all in-hospital activations. Intravenous thrombolysis was utilized in 8% of those with ischemic stroke; 3.4% were transferred for consideration of endovascular thrombectomy. In-hospital mortality was 17.7%, and the proportion of patients discharged to home was 34.4% for all activations.ConclusionThe in-hospital stroke mortality was high, and the proportions of patients who either received or were considered for acute intervention were low. Quality improvement targeting increased use of acute stroke intervention in eligible patients and reducing hospital mortality in this patient cohort is needed.
| S-EPMC8442154 | biostudies-literature
Project description:Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of <4.5 h duration who are eligible for IVT, tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS of <4.5 h duration who are eligible for IVT, we recommend against using tenecteplase at a dose of 0.40 mg/kg (low evidence, strong recommendation). For patients with AIS of <4.5 h duration with prehospital management with a mobile stroke unit who are eligible for IVT, we suggest tenecteplase 0.25 mg/kg over alteplase 0.90 mg/kg (low evidence, weak recommendation). For patients with large vessel occlusion (LVO) AIS of <4.5 h duration who are eligible for IVT, we recommend tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS on awakening from sleep or AIS of unknown onset who are selected with non-contrast CT, we recommend against IVT with tenecteplase 0.25 mg/kg (low evidence, strong recommendation). Expert consensus statements are also provided. Tenecteplase 0.25 mg/kg may be favoured over alteplase 0.9 mg/kg for patients with AIS of <4.5 h duration in view of comparable safety and efficacy data and easier administration. For patients with LVO AIS of <4.5 h duration who are IVT-eligible, IVT with tenecteplase 0.25 mg/kg is preferable over skipping IVT before MT, even in the setting of a direct admission to a thrombectomy-capable centre. IVT with tenecteplase 0.25 mg/kg may be a reasonable alternative to alteplase 0.9 mg/kg for patients with AIS on awakening from sleep or AIS of unknown onset and who are IVT-eligible after selection with advanced imaging.
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