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LOS ANGELES—Tenecteplase may be superior to alteplase for thrombolysis in patients with acute ischemic stroke who are scheduled to undergo thrombectomy, according to research presented at the International Stroke Conference 2018.
Comparing Two Thrombolytic Agents
The results came from the Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial, a multicenter study of 202 patients in Australia and New Zealand. It was conducted from 2015 to 2017 at 18 hospitals. All enrolled patients received thrombolytic treatment within 4.5 hours of stroke onset and underwent endovascular thrombectomy within six hours of onset.
Investigators examined patients’ blood flow after they had received thrombolysis and undergone an initial angiogram, but before they underwent thrombectomy. The proportion of patients with robust blood flow, which was defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus, was 22% in the patients treated with
After the researchers adjusted the data, they found that tenecteplase was associated with 2.6 times greater odds of robust reperfusion, compared with alteplase. The result was statistically significant for the noninferiority and superiority of tenecteplase, said Bruce C. Campbell, MBBS, PhD, Professor of Neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital. 
These results, however, failed to show a significant between-group difference for improvement in NIH Stroke Scale score at three days after enrollment. This outcome occurred in 72% of the patients who received tenecteplase and 69% of patients who received alteplase. The 90-day modified Rankin Scale score was 0 to 2 or unchanged from baseline in 65% of the tenecteplase group and 52% of the alteplase group, a difference that did not reach statistical significance. All patients who enrolled were selected to undergo thrombectomy if their angiogram showed continued occlusion. Dr. Campbell did not report the number of patients who underwent this intervention, however.
The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
Ongoing Research
Tenecteplase is a genetically modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half-life and allows for bolus administration, unlike alteplase, which needs continuous infusion. In the United States, the wholesale price per vial of tenecteplase is about $3,000 cheaper than that of alteplase, said Dr. Campbell.
Further data are needed before tenecteplase is ready for routine use, said Dr. Campbell. Two studies in progress are comparing tenecteplase with alteplase in patients with acute ischemic stroke who will not undergo endovascular thrombectomy. Dr. Campbell is leading a study that compares 0.25-mg/kg and 0.40-mg/kg doses of tenecteplase.
“I don’t think the data [that Dr. Campbell reported] are sufficient to say that tenecteplase is equivalent to alteplase. This [question] was studied in a select group of patients who had large-vessel occlusions and were transported to receive mechanical thrombectomy,” said William J. Powers, MD, Professor and Chair of Neurology at the University of North Carolina in Chapel Hill, who was not involved in the study. Most of the data on the efficacy of thrombolysis in patients with ischemic stroke have involved alteplase, he noted. Tenecteplase has FDA marketing approval only for treating patients with an acute myocardial infarction. Alteplase has FDA approval for treating acute ischemic stroke. Both drugs are marketed by Genentech.
Reports in recent years have suggested that treatment with tenecteplase appears to be at least as good as treatment with alteplase in patients with ischemic stroke. For example, a randomized trial that included 75 patients with ischemic stroke selected by imaging at three Australian centers found that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average five-point improvement in NIH Stroke Scale score.
In addition, results from the NOR-TEST study showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0 to 1 was achieved by 64% of patients who received tenecteplase and 63% of patients who received alteplase.
In the EXTEND-IA TNK trial, tenecteplase appeared to act better than alteplase and had the extra advantage of being administered as a bolus injection, said Jeffrey L. Saver, MD, Professor of Neurology and Director of the Stroke Unit at the University of California, Los Angeles, in an interview at the meeting. “Alteplase is delivered as a drip, and it is often hard to get patients with an IV infusion out of the hospital quickly when you have to transport the patient. You need a nurse in the ambulance monitoring the drip. With tenecteplase, you administer the bolus and can then send the patient without an IV line, said Dr. Saver, who was not involved in the EXTEND-IA TNK study.
“Two other trials of tenecteplase, compared with alteplase, are now underway, so we will soon have a much larger evidence base for tenecteplase. This is the first large, multicenter, randomized trial to show an advantage for tenecteplase, but it failed to show a significant advantage for change in NIH Stroke Scale score. The results show a strong signal of benefit, but we need additional data from other trials.”
—Mitchel L. Zoler
Suggested Reading
Campbell BC, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study. Int J Stroke. 2017 Sep 27 [Epub ahead of print].
Logallo N, Kvistad CE, Thomassen L. Therapeutic potential of tenecteplase in the management of acute ischemic stroke. CNS Drugs. 2015;29(10):811-818.
Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017;16(10):781-788.
Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Eng J Med. 2012;366(12):1099-1107.
LOS ANGELES—Tenecteplase may be superior to alteplase for thrombolysis in patients with acute ischemic stroke who are scheduled to undergo thrombectomy, according to research presented at the International Stroke Conference 2018.
Comparing Two Thrombolytic Agents
The results came from the Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial, a multicenter study of 202 patients in Australia and New Zealand. It was conducted from 2015 to 2017 at 18 hospitals. All enrolled patients received thrombolytic treatment within 4.5 hours of stroke onset and underwent endovascular thrombectomy within six hours of onset.
Investigators examined patients’ blood flow after they had received thrombolysis and undergone an initial angiogram, but before they underwent thrombectomy. The proportion of patients with robust blood flow, which was defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus, was 22% in the patients treated with
After the researchers adjusted the data, they found that tenecteplase was associated with 2.6 times greater odds of robust reperfusion, compared with alteplase. The result was statistically significant for the noninferiority and superiority of tenecteplase, said Bruce C. Campbell, MBBS, PhD, Professor of Neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.
These results, however, failed to show a significant between-group difference for improvement in NIH Stroke Scale score at three days after enrollment. This outcome occurred in 72% of the patients who received tenecteplase and 69% of patients who received alteplase. The 90-day modified Rankin Scale score was 0 to 2 or unchanged from baseline in 65% of the tenecteplase group and 52% of the alteplase group, a difference that did not reach statistical significance. All patients who enrolled were selected to undergo thrombectomy if their angiogram showed continued occlusion. Dr. Campbell did not report the number of patients who underwent this intervention, however.
The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
Ongoing Research
Tenecteplase is a genetically modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half-life and allows for bolus administration, unlike alteplase, which needs continuous infusion. In the United States, the wholesale price per vial of tenecteplase is about $3,000 cheaper than that of alteplase, said Dr. Campbell.
Further data are needed before tenecteplase is ready for routine use, said Dr. Campbell. Two studies in progress are comparing tenecteplase with alteplase in patients with acute ischemic stroke who will not undergo endovascular thrombectomy. Dr. Campbell is leading a study that compares 0.25-mg/kg and 0.40-mg/kg doses of tenecteplase.
“I don’t think the data [that Dr. Campbell reported] are sufficient to say that tenecteplase is equivalent to alteplase. This [question] was studied in a select group of patients who had large-vessel occlusions and were transported to receive mechanical thrombectomy,” said William J. Powers, MD, Professor and Chair of Neurology at the University of North Carolina in Chapel Hill, who was not involved in the study. Most of the data on the efficacy of thrombolysis in patients with ischemic stroke have involved alteplase, he noted. Tenecteplase has FDA marketing approval only for treating patients with an acute myocardial infarction. Alteplase has FDA approval for treating acute ischemic stroke. Both drugs are marketed by Genentech.
Reports in recent years have suggested that treatment with tenecteplase appears to be at least as good as treatment with alteplase in patients with ischemic stroke. For example, a randomized trial that included 75 patients with ischemic stroke selected by imaging at three Australian centers found that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average five-point improvement in NIH Stroke Scale score.
In addition, results from the NOR-TEST study showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0 to 1 was achieved by 64% of patients who received tenecteplase and 63% of patients who received alteplase.
In the EXTEND-IA TNK trial, tenecteplase appeared to act better than alteplase and had the extra advantage of being administered as a bolus injection, said Jeffrey L. Saver, MD, Professor of Neurology and Director of the Stroke Unit at the University of California, Los Angeles, in an interview at the meeting. “Alteplase is delivered as a drip, and it is often hard to get patients with an IV infusion out of the hospital quickly when you have to transport the patient. You need a nurse in the ambulance monitoring the drip. With tenecteplase, you administer the bolus and can then send the patient without an IV line, said Dr. Saver, who was not involved in the EXTEND-IA TNK study.
“Two other trials of tenecteplase, compared with alteplase, are now underway, so we will soon have a much larger evidence base for tenecteplase. This is the first large, multicenter, randomized trial to show an advantage for tenecteplase, but it failed to show a significant advantage for change in NIH Stroke Scale score. The results show a strong signal of benefit, but we need additional data from other trials.”
—Mitchel L. Zoler
Suggested Reading
Campbell BC, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study. Int J Stroke. 2017 Sep 27 [Epub ahead of print].
Logallo N, Kvistad CE, Thomassen L. Therapeutic potential of tenecteplase in the management of acute ischemic stroke. CNS Drugs. 2015;29(10):811-818.
Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017;16(10):781-788.
Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Eng J Med. 2012;366(12):1099-1107.
LOS ANGELES—Tenecteplase may be superior to alteplase for thrombolysis in patients with acute ischemic stroke who are scheduled to undergo thrombectomy, according to research presented at the International Stroke Conference 2018.
Comparing Two Thrombolytic Agents
The results came from the Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial, a multicenter study of 202 patients in Australia and New Zealand. It was conducted from 2015 to 2017 at 18 hospitals. All enrolled patients received thrombolytic treatment within 4.5 hours of stroke onset and underwent endovascular thrombectomy within six hours of onset.
Investigators examined patients’ blood flow after they had received thrombolysis and undergone an initial angiogram, but before they underwent thrombectomy. The proportion of patients with robust blood flow, which was defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus, was 22% in the patients treated with
After the researchers adjusted the data, they found that tenecteplase was associated with 2.6 times greater odds of robust reperfusion, compared with alteplase. The result was statistically significant for the noninferiority and superiority of tenecteplase, said Bruce C. Campbell, MBBS, PhD, Professor of Neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.
These results, however, failed to show a significant between-group difference for improvement in NIH Stroke Scale score at three days after enrollment. This outcome occurred in 72% of the patients who received tenecteplase and 69% of patients who received alteplase. The 90-day modified Rankin Scale score was 0 to 2 or unchanged from baseline in 65% of the tenecteplase group and 52% of the alteplase group, a difference that did not reach statistical significance. All patients who enrolled were selected to undergo thrombectomy if their angiogram showed continued occlusion. Dr. Campbell did not report the number of patients who underwent this intervention, however.
The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
Ongoing Research
Tenecteplase is a genetically modified tissue plasminogen activator with enhanced fibrin specificity that increases the drug’s half-life and allows for bolus administration, unlike alteplase, which needs continuous infusion. In the United States, the wholesale price per vial of tenecteplase is about $3,000 cheaper than that of alteplase, said Dr. Campbell.
Further data are needed before tenecteplase is ready for routine use, said Dr. Campbell. Two studies in progress are comparing tenecteplase with alteplase in patients with acute ischemic stroke who will not undergo endovascular thrombectomy. Dr. Campbell is leading a study that compares 0.25-mg/kg and 0.40-mg/kg doses of tenecteplase.
“I don’t think the data [that Dr. Campbell reported] are sufficient to say that tenecteplase is equivalent to alteplase. This [question] was studied in a select group of patients who had large-vessel occlusions and were transported to receive mechanical thrombectomy,” said William J. Powers, MD, Professor and Chair of Neurology at the University of North Carolina in Chapel Hill, who was not involved in the study. Most of the data on the efficacy of thrombolysis in patients with ischemic stroke have involved alteplase, he noted. Tenecteplase has FDA marketing approval only for treating patients with an acute myocardial infarction. Alteplase has FDA approval for treating acute ischemic stroke. Both drugs are marketed by Genentech.
Reports in recent years have suggested that treatment with tenecteplase appears to be at least as good as treatment with alteplase in patients with ischemic stroke. For example, a randomized trial that included 75 patients with ischemic stroke selected by imaging at three Australian centers found that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average five-point improvement in NIH Stroke Scale score.
In addition, results from the NOR-TEST study showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0 to 1 was achieved by 64% of patients who received tenecteplase and 63% of patients who received alteplase.
In the EXTEND-IA TNK trial, tenecteplase appeared to act better than alteplase and had the extra advantage of being administered as a bolus injection, said Jeffrey L. Saver, MD, Professor of Neurology and Director of the Stroke Unit at the University of California, Los Angeles, in an interview at the meeting. “Alteplase is delivered as a drip, and it is often hard to get patients with an IV infusion out of the hospital quickly when you have to transport the patient. You need a nurse in the ambulance monitoring the drip. With tenecteplase, you administer the bolus and can then send the patient without an IV line, said Dr. Saver, who was not involved in the EXTEND-IA TNK study.
“Two other trials of tenecteplase, compared with alteplase, are now underway, so we will soon have a much larger evidence base for tenecteplase. This is the first large, multicenter, randomized trial to show an advantage for tenecteplase, but it failed to show a significant advantage for change in NIH Stroke Scale score. The results show a strong signal of benefit, but we need additional data from other trials.”
—Mitchel L. Zoler
Suggested Reading
Campbell BC, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study. Int J Stroke. 2017 Sep 27 [Epub ahead of print].
Logallo N, Kvistad CE, Thomassen L. Therapeutic potential of tenecteplase in the management of acute ischemic stroke. CNS Drugs. 2015;29(10):811-818.
Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017;16(10):781-788.
Parsons M, Spratt N, Bivard A, et al. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Eng J Med. 2012;366(12):1099-1107.