Tenecteplase Matches Up Well With Alteplase in Acute Stroke: TRACE-2

When treating patients with acute ischemic stroke within 4.5 hours of symptom onset, tenecteplase provides noninferior outcomes compared with alteplase (Activase; Genentech), with similar safety, according to the randomized TRACE-2 trial. The study provides more evidence to support the growing use of tenecteplase in this setting.

At 90 days, the proportion of patients with a modified Rankin Scale (mRS) score of 0 to 1, the primary outcome, was 62% in the tenecteplase group and 58% in the alteplase group (RR 1.07; 95% CI 0.98-1.16), a difference that met criteria for noninferiority with a margin of 0.937, but not superiority, Shuya Li, MD (Beijing Tiantan Hospital, China), reported last week at the International Stroke Conference in Dallas, TX. There were no significant differences in safety outcomes.

The results, published simultaneously online in the Lancet, indicate that “intravenous tenecteplase may be used as an alternative to alteplase in patients with acute ischemic stroke within 4.5 hours of onset,” Li concluded.

IV thrombolysis with alteplase has been the backbone of acute stroke treatment for 25 years, noted Bijoy Menon, MD (Hotchkiss Brain Institute, University of Calgary, Canada), lead author of an accompanying editorial. Although endovascular thrombectomy has been established as the standard of care for patients with large-vessel occlusions, the procedure doesn’t work for everyone, he noted.

We now have—I would call it—reasonably robust evidence that we could actually use tenecteplase in our practice. Bijoy Menon

Thus, there remains an important role for IV thrombolytics, Menon commented to TCTMD, adding that tenecteplase, a genetically modified form of alteplase already approved for use in acute MI (TNKase; Genentech), has some advantages over its predecessor. It sticks to clots longer than alteplase does, potentially reduces the consumption of fibrinogen in the body, and possibly lessens bleeding risk, he said.

The major advantage, however, is that it can be delivered as a single bolus over 5 to 10 seconds, whereas alteplase is administered with an initial bolus followed by an hour-long infusion. That has implications for both ease of use in the hospital and for transfer between centers if a patient needs to be moved for thrombectomy, Menon explained.

It's also likely that using tenecteplase instead of alteplase will save money due to a lower cost per dose. One prior study estimated a pharmacy cost savings of about $400,000 over 1 year at a single center.

Several phase II trials and some phase III trials comparing tenecteplase and alteplase have been conducted over the years. Most recently, Menon and his colleagues reported the results of the Canadian AcT trial, demonstrating noninferior efficacy and similar safety with tenecteplase.

Now, TRACE-2 helps confirm those findings in a Chinese population, he said. With these trials, and the studies before them, “we now have—I would call it—reasonably robust evidence that we could actually use tenecteplase in our practice,” Menon said, noting that European and Canadian stroke guidelines have changed to recommend using the drug. US guidelines have not yet changed, but many centers already have begun switching over to tenecteplase, Menon added.

The TRACE-2 Trial

TRACE-2 was a noninferiority trial conducted at 53 sites across China. Investigators randomized 1,430 patients (median age about 66; 31% women) who had acute ischemic stroke and could be treated within 4.5 hours of symptom onset with tenecteplase 0.25 mg/kg (maximum dose 25 mg) or alteplase 0.9 mg/kg (maximum dose 90 mg). Median NIHSS score at baseline was 7.

The primary outcome was the proportion of patients with an excellent functional outcome (mRS 0-1) at 90 days; tenecteplase was shown to be noninferior to alteplase. Moreover, there were no significant differences across various secondary outcomes, including 90-day functional endpoints, early neurological outcomes, quality of life, and performance of activities of daily living.

In addition, there were no significant differences on safety outcomes, including symptomatic intracranial hemorrhage at 36 hours (2% in each group; P = 0.72) and at 90 days (2% in each group; P = 0.74). The death rate at 90 days was 7% in the tenecteplase group and 5% in the alteplase group (P = 0.22).

Making the Switch

At this point, Menon said, “I don’t see any reason why centers should not be using tenecteplase. Purely from an evidence perspective, I think we now have reasonable evidence to say that we can actually use tenecteplase.”

He acknowledged, however, that there could be some barriers to making the switch from alteplase to tenecteplase in some parts of the world, even beyond the typical adoption curve for new interventions that sees early, intermediate, and late adopters.

In North America, there is a sufficient supply of tenecteplase that allows centers to starting using it if they choose, but in Europe, there is currently a supply issue that is expected to be resolved in a year or two, Menon said.

Once that is addressed, there will be a continuing migration to tenecteplase for acute stroke treatment in the coming years, he predicted, adding that the move will be accelerated once regulators sign on; tenecteplase is still used off-label for stroke.

Many patients eligible for IV thrombolysis are not treated, “and this easy-to-use drug is just going to be a significant boost to acute stroke care and to patients,” Menon said. “Stroke is still the leading cause of disability, so it’s very important that more and more patients receive this treatment.”