LOS ANGELES — Not only is tenecteplase a cheaper and more convenient thrombolytic agent than alteplase, but new research suggests it also leads to better outcomes in stroke patients selected for endovascular thrombectomy.
“Ours was a noninferiority hypothesis because we felt that if you could show that tenecteplase is at least as good as alteplase, then the convenience and cost would justify a switch,” said Bruce C. Campbell, PhD, a stroke neurologist at Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
But in terms of reperfusion, the study showed that “tenecteplase wasn’t just noninferior; it was superior,” said Dr Campbell.
Tenecteplase is a genetically modified tissue plasminogen activator (tPA) that has enhanced fibrin specificity. It has a relatively long half-life, which allows single-bolus administration.
The agent is not approved in the United States for use in stroke; it is approved only for the treatment of myocardial infarction. Alteplase, on the other hand, is approved for acute ischemic stroke and myocardial infarction.
The trial, EXTEND-IA TNK, was presented here at the International Stroke Conference (ISC) 2018.
While some previous studies showed trends toward improved clinical outcomes with tenecteplase compared with alteplase, results were not statistically significant, said Dr Campbell.
The new study included 202 adult patients from 13 centers in Australia and New Zealand who were randomly assigned to receive tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg) within 4.5 hours of an ischemic stroke. All patients had a large-vessel occlusion (internal carotid, basilar, or middle cerebral artery) and had been selected for endovascular thrombectomy.
The mean age of study participants was about 71 years, and over half were male. Prestroke modified Rankin Scale (mRS) score was 3 or less (ie, patients were not severely disabled). Median National Institutes of Health Stroke Scale (NIHSS) score was 17.
The primary outcome was the percentage of substantial reperfusion at initial catheter angiogram, assessed by blinded core laboratory as modified Treatment In Cerebral Infarction grade of 2b/3 or the absence of retrievable thrombus.
The design included sequential testing of noninferiority (a margin of 2.3%), followed by test of superiority if noninferiority was demonstrated.
Doubled Rate
In terms of reperfusion, “the study showed that tenecteplase had double the percent than alteplase” (22% vs 10%), with a risk difference of 12% (0.12; 95% confidence interval [CI] 0.02-0.21), said Dr Campbell.
He noted that the adjusted odds ratio was 2.6 {95% CI, 1.1 – 5.9; non-inferiority, P = .002; superiority, P = .02).
As for secondary outcomes, the 90-day mRS score favored tenecteplase (odds ratio, 1.7), which was somewhat surprising to the researchers, said Dr Campbell.
“We didn’t expect a huge difference in the Rankin because everybody was going on to thrombectomy, but as it turned out, there was a significant shift.”
The percentages for mRS score of 0 to 2 or no change from baseline were 65% with tenecteplase vs 52% with alteplase (P = .06), and those for mRS score of 0 to 1 or no change from baseline were 52% vs 43%, respectively (P = .23).
“So tenecteplase does seem to improve outcomes, although the trend for independence was not quite there,” said Dr Campbell.
Neurologic recovery up to 72 hours, as assessed by a reduction of 8 or more NIHSS points, or reaching an mRS score of 0 to 1 by day 3, was about the same in both groups (72% for tenecteplase vs 69% for alteplase; P = .66).
The study did not uncover any safety concerns. There was only one symptomatic intracerebral hemorrhage in each group, and the trend for mortality “was in the right direction” (10% for tenecteplase vs 18% in the alteplase group; P = .08), said Dr Campbell.
Attractive Alternative
He concluded that tenecteplase “is a very attractive alternative to alteplase prior to thrombectomy,” although further research is still needed.
“We need to work very hard on testing this agent further, and getting regulatory approval for this indication if it continues to prove effective,” he told Medscape Medical News. He added that “the bulk” of stroke patients still get thrombolysis and that this agent “is something that can be delivered in any hospital.”
Tenecteplase is about $3000 cheaper per case than alteplase; it is priced at around $5800, compared with $8800 for alteplase, noted Dr Campbell. As well, he said, while alteplase takes about an hour to infuse, tenecteplase can be given “in 10 seconds.”
This contributes to its convenience. “With alteplase, if you need to put patients in an ambulance, you have to take the infusion pump with you. Sometimes you can’t transport them at all while they’re having the infusion, depending on the system.”
Ongoing trials with this agent include the TASTE trial and ATTEST-2, which are testing 0.25 mg/kg of tenecteplase in non endovascular patients, and EXTEND-IA TNK part 2, which is comparing tenecteplase doses of 0.40 to 0.25 mg/kg of before endovascular thrombectomy (NCT03340493).
Medscape Medical News invited Bruce Ovbiagele, MD, professor and chair of neurology, Medical School of South Carolina, Charleston, who chaired the media briefing at which the study was discussed, to comment on these new findings.
He called them “very exciting” and “very promising.”
“The fact that the design was to show noninferiority but the study actually showed superiority was very, very impressive,” said Dr Ovbiagele.
The finding that more patients receiving tenecteplase than those receiving alteplase no longer needed to get the thrombectomy is “huge,” he said.
Being able to give the agent as a bolus “is very helpful,” noted Dr Ovbiagele. He added that not having to deal with transporting a patient still receiving tPA is an important advantage.
The new results, which are more “robust” and “impressive” than those of previous trials, might be enough to convince the medical community that tenecteplase is the way to go, said Dr Ovbiagele.
“I would hope that the tide is going to start to turn,” he said, referring to the two other trials that are still ongoing. “With this study and maybe at least one of these other ones, I think we’re going to see a change.”
The study received support from Medtronic and from other groups. The researchers have disclosed no relevant financial relationships.
International Stroke Conference (ISC) 2018. Late Breaking Abstract 2. Presented January 24, 2018.
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