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Bruce C V Campbell - One of the best experts on this subject based on the ideXlab platform.
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routine use of Tenecteplase for thrombolysis in acute ischemic stroke
Stroke, 2021Co-Authors: Cathy S Zhong, Bruce C V Campbell, James Beharry, Duncan Wilson, Daniel Salazar, Kelly Smith, Stephen Withington, Campbell Le Heron, Deborah F Mason, Roderick DuncanAbstract:Background and Purpose: In ischemic stroke, intravenous Tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand change...
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determining the optimal dose of Tenecteplase before endovascular therapy for ischemic stroke extend ia tnk part 2 a multicenter randomized controlled study
International Journal of Stroke, 2020Co-Authors: Timothy J. Kleinig, Bruce C V Campbell, Peter Mitchell, Leonid Churilov, Nawaf Yassi, Vincent Thijs, Bernard YanAbstract:Background and hypothesisIntravenous thrombolysis with Tenecteplase is more effective than alteplase in achieving substantial reperfusion at initial angiographic assessment and improves functional ...
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dabigatran reversal before intravenous Tenecteplase in acute ischemic stroke
Stroke, 2020Co-Authors: James Beharry, Mark W Parsons, Bruce C V Campbell, Michael J Waters, Roy Drew, John N Fink, Duncan Wilson, Timothy J. KleinigAbstract:Background and Purpose- Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous Tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before Tenecteplase thrombolysis for acute ischemic stroke. Methods- We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous Tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results- We identified 13 patients receiving intravenous Tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69-85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4-21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57-113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with Tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0-2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions- Our experience suggests intravenous thrombolysis with Tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.
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Tenecteplase for the treatment of acute ischemic stroke a review of completed and ongoing randomized controlled trials
International Journal of Stroke, 2018Co-Authors: Shelagh B Coutts, Keith W. Muir, Bruce C V Campbell, Eivind Berge, Mark W ParsonsAbstract:Alteplase has been the mainstay of thrombolytic treatment since the National Institutes of Neurological Disorders and Stroke trial was published in 1995. Over recent years, several trials have investigated alternative thrombolytic agents. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, has a longer half-life, allowing single intravenous bolus administration without infusion, is more fibrin specific, produces less systemic depletion of circulating fibrinogen, and is more resistant to plasminogen activator inhibitor compared to alteplase. Tenecteplase is established as the first-line intravenous thrombolytic drug for myocardial infarction, where it has been shown to achieve comparable reperfusion with reduced risk of systemic bleeding in comparison to alteplase. We review the literature on Tenecteplase for the treatment of acute ischemic stroke, with a focus on the major completed and ongoing trials. Overall, Tenecteplase shows promise for treatment of acute ischemic stroke, both in populations currently eligible for alteplase and also in groups not currently treated with thrombolysis.
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Tenecteplase versus alteplase before thrombectomy for ischemic stroke
The New England Journal of Medicine, 2018Co-Authors: Bruce C V Campbell, Timothy J. Kleinig, Peter Mitchell, Leonid Churilov, Nawaf Yassi, Richard Dowling, Steven Bush, Helen M Dewey, Vincent ThijsAbstract:Abstract Background Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. Methods We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive Tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of Tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologi...
Xuya Huang - One of the best experts on this subject based on the ideXlab platform.
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Tenecteplase in ischemic stroke offers improved recanalization analysis of 2 trials
Neurology, 2017Co-Authors: Andrew Bivard, Bharath Kumar Cheripelli, Dheeraj Kalladka, Ian Ford, Xuya Huang, Neil J Spratt, Christopher R Levi, Bruce C V Campbell, Fiona Moreton, Christopher F BladinAbstract:Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with Tenecteplase compared to alteplase. Methods: Pooled clinical and imaging data from 2 phase 2 randomized trials comparing Tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs). Results: From 146 pooled patients, 69 had a TICI 0/1 occlusion overall at baseline. Tenecteplase-treated patients with a complete vessel occlusion had greater complete recanalization rates at 24 hours (71% for Tenecteplase vs 43% for alteplase, p p = 0.001) and higher rates of favorable 90-day outcomes (mRS 0–1 of Tenecteplase compared with alteplase, OR 4.82, 95% confidence interval 1.02–7.84, p = 0.05). Conclusions: Tenecteplase may offer greater recanalization efficacy compared to alteplase, possibly exaggerated in patients with complete vessel occlusions on baseline CTA.
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impact of computed tomography perfusion imaging on the response to Tenecteplase in ischemic stroke analysis of 2 randomized controlled trials
Circulation, 2017Co-Authors: Andrew Bivard, Bharath Kumar Cheripelli, Dheeraj Kalladka, Ian Ford, Xuya Huang, Christopher R Levi, Bruce C V Campbell, Fiona Moreton, Patrick Mcelduff, Christopher F BladinAbstract:Background:We pooled 2 clinical trials of Tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of Tenecteplase and the other that showed ...
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Tenecteplase versus alteplase in stroke thrombolysis an individual patient data meta analysis of randomized controlled trials
International Journal of Stroke, 2016Co-Authors: Xuya Huang, Christopher R Levi, Rachael L Macisaac, John L P Thompson, Bruce Levin, Richard Buchsbaum, Clarke E Haley, Bruce C V Campbell, Christopher F Bladin, Mark W ParsonsAbstract:BackgroundTenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis.AimsWe undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with Tenecteplase in acute stroke.MethodsEligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of Tenecteplase and alteplase.ResultsThree relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of Tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of Tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest...
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Tenecteplase and alteplase in acute ischaemic stroke thrombolysis : clinical and imaging study
2016Co-Authors: Xuya HuangAbstract:Introduction: Intravenous thrombolysis in acute ischaemic stroke with alteplase improves clinical outcomes, but it has limited efficacy and is associated with increased risk of intracranial haemorrhage. An improved tissue plasminogen activator, Tenecteplase, was evidenced to be at least equally effective with lower risk of haemorrhage in acute myocardial infarction thrombolysis. To date, two completed phase II randomised controlled studies comparing Tenecteplase and alteplase in acute ischaemic strokes showed variable results. Methods: A literature review of thrombolytic agents used in myocardial infarction and acute ischaemic stroke was performed, followed by a retrospective investigation of the bolus-to- infusion delay of alteplase administration. The main focus of this thesis is the report of our single centre phase II randomised controlled trial that compared Tenecteplase (0.25mg/kg, maximum 25mg) and alteplase (0.9mg/kg, maximum 90mg, 10% as the initial bolus, following by one hour infusion with the rest of the dose) in acute ischaemic stroke thrombolysis using advanced imaging as biomarkers. Imaging comprised baseline computed tomography (CT), CT perfusion (CTP) and CT angiography (CTA), and CT+CTA at 24-48 hours. The primary end-point was penumbral salvage (CTP-defined penumbra volume minus follow-up CT infarct volume). A sub-study of coagulation and fibrinolysis analysis of the two agents was performed by comparing a group of coagulation variables measured pre-treatment, 3-12 hours, and 24±3 hours post thrombolysis. An individual patient data (IPD) meta-analysis was carried out using all three completed Tenecteplase/alteplase comparison studies in stroke thrombolysis. We compared clinical outcomes including modified Rankin scale at 3 months, early neurological improvement at 24 hours, intracerebral haemorrhage rate and mortality at 3 months between all three Tenecteplase doses (0.1mg/kg, 0.25 mg/kg, and 0.4mg/kg) examined and standard alteplase. Imaging outcomes including penumbra salvage, recanalisation rates were also compared using the data from the two studies that had advance imaging carried out. Results: Delay between the initial bolus and the subsequent infusion in administration of alteplase is common. This may reduce the likelihood of achieving a good functional outcome. Among the 104 patients recruited in ATTEST trial, 71 contributed to the imaging primary outcome. No significant differences were observed for penumbral salvage [68 (SD 28) % Tenecteplase vs 68 (SD 23) % alteplase], mean difference 1% (95% confidence interval -10%, 12%, p=0·81) or for any secondary end-point. The SICH incidence (1/52, 2% vs 2/51, 4%, by SITS-MOST definition, p=0·55; by ECASS-2 definition, 3/52, 6% Tenecteplase vs 4/51, 8% alteplase, p=0.59) did not differed significantly. There was a trend towards lower ICH risk in the Tenecteplase group (8/52 Tenecteplase, 15% vs 14/51 alteplase, 29%, p=0·091). Compared to baseline, alteplase caused significant hypofibrinogenaemia (p=0.002), prolonged Prothrombin Time (PT) (p=0.011), hypoplasminogenaemia (p=0.001) and lower Factor V (p=0.002) at 3-12 hours after administration with persistent hypofibrinogenaemia at 24h (p=0.011), while only minor hypoplasminogenaemia (P=0.029) was seen in the Tenecteplase group. Tenecteplase consumed less plasminogen (p
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coagulation and fibrinolytic activity of Tenecteplase and alteplase in acute ischemic stroke
Stroke, 2015Co-Authors: Xuya Huang, Bharath Kumar Cheripelli, Dheeraj Kalladka, Rachael L Macisaac, Fiona Moreton, Campbell R Tait, Keith W. MuirAbstract:Background and Purpose— We compared the fibrinolytic activity of Tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage. Methods— Venous blood samples from a subgroup of participants in the Alteplase–Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, d-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann–Whitney tests for between-group differences. Results— Thirty patients were included (alteplase=14 and Tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia ( P =0.002), prolonged prothrombin time ( P =0.011), hypoplasminogenaemia ( P =0.001), and lower factor V ( P =0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours ( P =0.011), whereas only minor hypoplasminogenaemia ( P =0.029) was seen in the Tenecteplase group. Tenecteplase consumed less plasminogen ( P <0.001) and fibrinogen ( P =0.002) compared with alteplase. Conclusions— In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas Tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with Tenecteplase in the ATTEST study. Clinical Trial Registration— URL: . Unique identifier: [NCT01472926][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01472926&atom=%2Fstrokeaha%2F46%2F12%2F3543.atom
Christopher F Bladin - One of the best experts on this subject based on the ideXlab platform.
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Tenecteplase in ischemic stroke offers improved recanalization analysis of 2 trials
Neurology, 2017Co-Authors: Andrew Bivard, Bharath Kumar Cheripelli, Dheeraj Kalladka, Ian Ford, Xuya Huang, Neil J Spratt, Christopher R Levi, Bruce C V Campbell, Fiona Moreton, Christopher F BladinAbstract:Objective: To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with Tenecteplase compared to alteplase. Methods: Pooled clinical and imaging data from 2 phase 2 randomized trials comparing Tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs). Results: From 146 pooled patients, 69 had a TICI 0/1 occlusion overall at baseline. Tenecteplase-treated patients with a complete vessel occlusion had greater complete recanalization rates at 24 hours (71% for Tenecteplase vs 43% for alteplase, p p = 0.001) and higher rates of favorable 90-day outcomes (mRS 0–1 of Tenecteplase compared with alteplase, OR 4.82, 95% confidence interval 1.02–7.84, p = 0.05). Conclusions: Tenecteplase may offer greater recanalization efficacy compared to alteplase, possibly exaggerated in patients with complete vessel occlusions on baseline CTA.
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impact of computed tomography perfusion imaging on the response to Tenecteplase in ischemic stroke analysis of 2 randomized controlled trials
Circulation, 2017Co-Authors: Andrew Bivard, Bharath Kumar Cheripelli, Dheeraj Kalladka, Ian Ford, Xuya Huang, Christopher R Levi, Bruce C V Campbell, Fiona Moreton, Patrick Mcelduff, Christopher F BladinAbstract:Background:We pooled 2 clinical trials of Tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of Tenecteplase and the other that showed ...
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Tenecteplase versus alteplase in stroke thrombolysis an individual patient data meta analysis of randomized controlled trials
International Journal of Stroke, 2016Co-Authors: Xuya Huang, Christopher R Levi, Rachael L Macisaac, John L P Thompson, Bruce Levin, Richard Buchsbaum, Clarke E Haley, Bruce C V Campbell, Christopher F Bladin, Mark W ParsonsAbstract:BackgroundTenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis.AimsWe undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with Tenecteplase in acute stroke.MethodsEligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of Tenecteplase and alteplase.ResultsThree relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of Tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of Tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest...
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a randomized trial of Tenecteplase versus alteplase for acute ischemic stroke
The New England Journal of Medicine, 2012Co-Authors: Mark W Parsons, Ferdinand Miteff, Neil J Spratt, Bruce C V Campbell, Christopher F Bladin, Andrew Bivard, Patrick Mcelduff, Kong Chung, Bill Obrien, Chris AllenAbstract:BackgroundIntravenous alteplase is the only approved treatment for acute ischemic stroke. Tenecteplase, a genetically engineered mutant tissue plasminogen activator, is an alternative thrombolytic agent. MethodsIn this phase 2B trial, we randomly assigned 75 patients to receive alteplase (0.9 mg per kilogram of body weight) or Tenecteplase (0.1 mg per kilogram or 0.25 mg per kilogram) less than 6 hours after the onset of ischemic stroke. To favor the selection of patients most likely to benefit from thrombolytic therapy, the eligibility criteria were a perfusion lesion at least 20% greater than the infarct core on computed tomographic (CT) perfusion imaging at baseline and an associated vessel occlusion on CT angiography. The coprimary end points were the proportion of the perfusion lesion that was reperfused at 24 hours on perfusion-weighted magnetic resonance imaging and the extent of clinical improvement at 24 hours as assessed on the National Institutes of Health Stroke Scale (NIHSS, a 42-point scale ...
Nicola Logallo - One of the best experts on this subject based on the ideXlab platform.
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clinical outcomes and safety profile of Tenecteplase in wake up stroke
Acta Neurologica Scandinavica, 2020Co-Authors: Hassan Khan Ahmed, Nicola Logallo, Lars Thomassen, Vojtech Novotny, Martin W Kurz, Sara Maria MathisenAbstract:BACKGROUND Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of Tenecteplase in wake-up stroke (WUPS). AIMS To investigate safety and efficacy of Tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. METHODS WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients randomly assigned (1:1) to receive intravenous Tenecteplase 0.4 mg/kg (to a maximum of 40 mg) or alteplase 0.9 mg/kg (to a maximum of 90 mg). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. RESULTS Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with Tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. CONCLUSIONS In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or Tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.
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Tenecteplase versus alteplase between 3 and 4 5 hours in low national institutes of health stroke scale
Stroke, 2019Co-Authors: Christopher Elnan Kvistad, Nicola Logallo, Vojtech Novotny, Ole Morten Ronning, Bente Thommessen, Hakon Tobro, Anne Hege AamodtAbstract:Background and Purpose- Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of Tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods- The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing Tenecteplase with alteplase. Results- The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2-6). In the intention-to-treat analysis, 57% of patients that received Tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0-1) at 3 months (odds ratio, 1.19; 95% CI, 0.68-2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the Tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26-2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the Tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65-2.37). Conclusions- Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.
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Tenecteplase versus alteplase for management of acute ischaemic stroke nor test a phase 3 randomised open label blinded endpoint trial
Lancet Neurology, 2017Co-Authors: Christopher Elnan Kvistad, Nicola Logallo, Vojtech Novotny, Ole Morten Ronning, Jorg Assmus, Lars AlteheldAbstract:Summary Background Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of Tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of Tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. Methods This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous Tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0–1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. Findings Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the Tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64–79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2–8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the Tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the Tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84–1·38; p=0·52). By 3 months, 29 (5%) patients had died in the Tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the Tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). Interpretation Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether Tenecteplase is non-inferior to alteplase. Funding Research Council of Norway.
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Therapeutic Potential of Tenecteplase in the Management of Acute Ischemic Stroke
CNS Drugs, 2015Co-Authors: Nicola Logallo, Christopher Elnan Kvistad, Lars ThomassenAbstract:Given that alteplase has been the only approved thrombolytic agent for acute ischemic stroke for almost two decades, there has been intense interest in more potent and safer agents over the last few years. Tenecteplase is a bioengineered mutation of alteplase with advantageous pharmacodynamics and pharmacokinetics. The superiority of Tenecteplase over alteplase has been proven by in vitro and animal studies, and it was approved for use in myocardial infarction more than a decade ago. In patients with acute ischemic stroke, Tenecteplase has shown promise in randomized phase II trials and the drug is currently being tested in four phase III clinical trials that will start delivering definite results in the near future: NOR-TEST (NCT01949948), TASTE (ACTRN12613000243718), TEMPO-2 (NCT02398656), and TALISMAN (NCT02180204).
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the norwegian Tenecteplase stroke trial nor test randomised controlled trial of Tenecteplase vs alteplase in acute ischaemic stroke
BMC Neurology, 2014Co-Authors: Christopher Elnan Kvistad, Nicola Logallo, Aliona Nacu, Halvor Naess, Ulrike WajeandreassenAbstract: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. 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. 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).
Christopher Elnan Kvistad - One of the best experts on this subject based on the ideXlab platform.
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safety and predictors of stroke mimics in the norwegian Tenecteplase stroke trial nor test
International Journal of Stroke, 2019Co-Authors: Christopher Elnan Kvistad, Vojtech Novotny, Halvor Naess, Ulrike Wajeandreassen, Guri Hagberg, Hege IhlehansenAbstract:BackgroundStroke mimics are frequently treated with thrombolysis in clinical practice and thrombolytic trials. Although alteplase in stroke mimics has proven to be safe, safety of Tenecteplase in s...
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safety and outcomes of Tenecteplase in moderate and severe ischemic stroke
Stroke, 2019Co-Authors: Christopher Elnan Kvistad, Vojtech Novotny, Martin W Kurz, Ole Morten Ronning, Bente ThommessenAbstract:Background and Purpose- Tenecteplase represents a promising alternative to alteplase as thrombolytic treatment in acute ischemic stroke. There are limited data on Tenecteplase 0.4 mg/kg in patients with increased stroke severity. We aimed to assess safety and efficacy of Tenecteplase 0.4 mg/kg in patients with moderate and severe ischemic stroke. Methods- NOR-TEST (Norwegian Tenecteplase Stroke Trial) was a phase III trial designed to investigate the safety and efficacy of Tenecteplase 0.4 mg/kg versus alteplase 0.9 mg/kg in ischemic stroke. In this post hoc analysis, moderate stroke was defined as admission National Institutes of Health Stroke Scale; 6 to 14 and severe stroke as National Institutes of Health Stroke Scale; ≥15. Rates of favorable outcome at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality after 7 and 90 days were assessed. Results- In patients with moderate stroke (n=261), there were no differences in rates of favorable outcome, sICH, or mortality between Tenecteplase and alteplase. In patients with severe stroke (n=87), there were no differences in outcome, frequency of sICH, or mortality at 7 days, but all-cause mortality at 90 days was increased in patients treated with Tenecteplase (10 [26.3%] versus 4 [9.1%]; P=0.045). One patient died of sICH in the Tenecteplase group, and 2 patients died of sICH in the alteplase group. Conclusions- Rates of favorable outcome and sICH were similar between treatment groups in patients with moderate and severe stroke. Mortality after 90 days was increased in patients with severe stroke receiving Tenecteplase. Future studies assessing Tenecteplase 0.4 mg/kg should monitor safety parameters closely in patients with severe stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.
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Tenecteplase versus alteplase between 3 and 4 5 hours in low national institutes of health stroke scale
Stroke, 2019Co-Authors: Christopher Elnan Kvistad, Nicola Logallo, Vojtech Novotny, Ole Morten Ronning, Bente Thommessen, Hakon Tobro, Anne Hege AamodtAbstract:Background and Purpose- Thrombolysis with alteplase has beneficial effect on outcome and is safe within 4.5 hours. The present study compares the efficacy and safety of Tenecteplase and alteplase in patients treated 3 to 4.5 hours after ischemic stroke. Methods- The data are from a prespecified substudy of patients included in The NOR-TEST (Norwegian Tenecteplase Stroke Trial), a randomized control trial comparing Tenecteplase with alteplase. Results- The median admission National Institutes of Health Stroke Scale for this study population was 3 (interquartile range, 2-6). In the intention-to-treat analysis, 57% of patients that received Tenecteplase and 53% of patients that received alteplase reached good functional outcome (modified Rankin Scale score of 0-1) at 3 months (odds ratio, 1.19; 95% CI, 0.68-2.10). The rates of intracranial hemorrhage in the first 48 hours were 5.7% in the Tenecteplase group and 6.7% in the alteplase group (odds ratio, 0.84; 95% CI, 0.26-2.70). At 3 months, mortality was 5.7% and 4.5%, respectively. After excluding stroke mimics and patients with modified Rankin Scale score of >1 before stroke, the proportion of patients with good functional outcome was 61% in the Tenecteplase group and 57% in the alteplase group (odds ratio, 1.24; 95% CI, 0.65-2.37). Conclusions- Tenecteplase is at least as effective as alteplase to achieve a good clinical outcome in patients with mild stroke treated between 3 and 4.5 hours after ischemic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.
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Tenecteplase versus alteplase for management of acute ischaemic stroke nor test a phase 3 randomised open label blinded endpoint trial
Lancet Neurology, 2017Co-Authors: Christopher Elnan Kvistad, Nicola Logallo, Vojtech Novotny, Ole Morten Ronning, Jorg Assmus, Lars AlteheldAbstract:Summary Background Tenecteplase is a newer thrombolytic agent with some pharmacological advantages over alteplase. Previous phase 2 trials of Tenecteplase in acute ischaemic stroke have shown promising results. We aimed to investigate the safety and efficacy of Tenecteplase versus alteplase in patients with acute stroke who were eligible for intravenous thrombolysis. Methods This phase 3, randomised, open-label, blinded endpoint, superiority trial was done in 13 stroke units in Norway. We enrolled adults with suspected acute ischaemic stroke who were eligible for thrombolysis and admitted within 4·5 h of symptom onset or within 4·5 h of awakening with symptoms, or who were eligible for bridging therapy before thrombectomy. Patients were randomly assigned (1:1) to receive intravenous Tenecteplase 0·4 mg/kg (to a maximum of 40 mg) or alteplase 0·9 mg/kg (to a maximum of 90 mg), via a block randomisation schedule stratified by centre of inclusion. Patients were not informed of treatment allocation; treating physicians were aware of treatment allocation but those assessing the primary and secondary endpoints were not. The primary outcome was excellent functional outcome defined as modified Rankin Scale (mRS) score 0–1 at 3 months. The primary analysis was an unadjusted and non-stratified intention-to-treat analysis with last observation carried forward for imputation of missing data. This study is registered with ClinicalTrials.gov, number NCT01949948. Findings Between Sept 1, 2012, and Sept 30, 2016, 1107 patients met the inclusion criteria and seven patients were excluded because informed consent was withdrawn or eligibility for thrombolytic treatment was reconsidered. 1100 patients were randomly assigned to the Tenecteplase (n=549) or alteplase (n=551) groups. The median age of participants was 77 years (IQR 64–79) and the median National Institutes of Health Stroke Scale score at baseline was 4 points (IQR 2–8). A final diagnosis other than ischaemic stroke or transient ischaemic attack was found in 99 (18%) patients in the Tenecteplase group and 91 (17%) patients in the alteplase group. The primary outcome was achieved by 354 (64%) patients in the Tenecteplase group and 345 (63%) patients in the alteplase group (odds ratio 1·08, 95% CI 0·84–1·38; p=0·52). By 3 months, 29 (5%) patients had died in the Tenecteplase group compared with 26 (5%) in the alteplase group. The frequency of serious adverse events was similar between groups (145 [26%] in the Tenecteplase group vs 141 [26%] in the alteplase group; p=0·74). Interpretation Tenecteplase was not superior to alteplase and showed a similar safety profile. Most patients enrolled in this study had mild stroke. Further trials are needed to establish the safety and efficacy in patients with severe stroke and whether Tenecteplase is non-inferior to alteplase. Funding Research Council of Norway.
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Therapeutic Potential of Tenecteplase in the Management of Acute Ischemic Stroke
CNS Drugs, 2015Co-Authors: Nicola Logallo, Christopher Elnan Kvistad, Lars ThomassenAbstract:Given that alteplase has been the only approved thrombolytic agent for acute ischemic stroke for almost two decades, there has been intense interest in more potent and safer agents over the last few years. Tenecteplase is a bioengineered mutation of alteplase with advantageous pharmacodynamics and pharmacokinetics. The superiority of Tenecteplase over alteplase has been proven by in vitro and animal studies, and it was approved for use in myocardial infarction more than a decade ago. In patients with acute ischemic stroke, Tenecteplase has shown promise in randomized phase II trials and the drug is currently being tested in four phase III clinical trials that will start delivering definite results in the near future: NOR-TEST (NCT01949948), TASTE (ACTRN12613000243718), TEMPO-2 (NCT02398656), and TALISMAN (NCT02180204).
