LOS ANGELES – Thrombolysis with tenecteplase beat alteplase on an acute imaging endpoint in patients with acute ischemic stroke who were on their way to also get thrombectomy in a randomized, multicenter study with 202 patients in Australia and New Zealand.
The results of the trial, called Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK), showed that when the patients underwent their initial angiogram after receiving thrombolysis and before their thrombectomy procedure, the percentage of patients with robust blood flow – a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3 or no retrievable thrombus – was 22% in the patients treated with tenecteplase 0.25 mg/kg and 10% among those who received alteplase 0.9 mg/kg. After adjustment, the 12% incremental change in robust reperfusion with tenecteplase calculated into a 2.6-fold higher rate of robust reperfusion, statistically significant for both noninferiority and for superiority, , said at the International Stroke Conference, sponsored by the American Heart Association.
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 (CNS Drugs. 2015 Oct; ). Tenecteplase also has a U.S. wholesale price that is about $3,000 cheaper per vial than alteplase, said Dr. Campbell, professor of neurology at the University of Melbourne and head of hyperacute stroke at Royal Melbourne Hospital.
But further data are needed before tenecteplase is ready for routine use, conceded Dr. Campbell, an assessment other experts agreed with. Dr. Campbell cited two studies in progress that are comparing tenecteplase with alteplase in acute ischemic stroke patients not headed for endovascular thrombectomy, as well as a study he is leading that compares the tenecteplase dose he just tested, 0.25 mg/kg, with a higher dose, 0.40 mg/kg.(TNKase) has Food and Drug Administration marketing only for treating patients with an acute MI. Alteplase (Activase) has FDA for treating acute ischemic stroke. Both drugs are marketed by Genentech.
Several reports have appeared in recent years suggesting that treatment with tenecteplase seems to be at least as good as alteplase in ischemic stroke patients. For example, a randomized trial with 75 ischemic stroke patients selected by imaging at three Australian centers showed that treatment with tenecteplase produced a significant 24% improvement in the rate of arterial reperfusion and an average 5-point improvement in NIH Stroke Scale score (N Engl J Med. 2012;). And results from the study recently showed that among 1,100 patients randomized at 13 Norwegian centers, the primary outcome of a 90-day modified Rankin Scale score of 0-1 was achieved by 64% of the tenecteplase patients and by 63% of those who received alteplase (Lancet Neurol. 2017 Oct; ).
The EXTEND-IA TNK trial ran during 2015-2017 at 18 hospitals. All enrolled patients received their thrombolytic treatment within 4.5 hours of their stroke onset, and underwent endovascular thrombectomy within 6 hours of onset. The safety outcomes of death, symptomatic intracranial hemorrhage, and parenchymal hematoma occurred at statistically similar rates in both treatment arms.
The study was investigator initiated and funded chiefly by the Australian government. Medtronic provided an unrestricted grant for trial infrastructure but had no role in study design conduct or analysis. Dr. Campbell and Dr. Powers had no disclosures.
SOURCE: Campbell B et al. ISC 2018, abstract .