Tenecteplase Noninferior to Alteplase for Ischemic Stroke: TRACE-2

Tenecteplase is as effective as alteplase with respect to disability outcomes and safety in Chinese patients with ischemic stroke, a new study has found.

Dr Shuya Li

“This was a pivotal trial in establishing the safety and efficacy of tenecteplase as an alternative to alteplase in the thrombolytic treatment of acute ischemic stroke within 4.5 hours in Asian patients,” study author Shuya Li, MD, associate chief physician, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, told Medscape Medical News.

The findings in this all-Chinese population should have an impact on the use of tenecteplase going forward, said Li. “The results provide further evidence to support a worldwide switch to tenecteplase as the preferred thrombolytic for acute ischemic stroke.”

The findings were presented at the International Stroke Conference (ISC) 2023.

Single Bolus

Use of alteplase (tissue plasminogen activator [tPA]) has for years been the main approach to thrombolytic reperfusion therapy for acute stroke patients, but tenecteplase has recently emerged as a potential successor.

Tenecteplase is a tPA produced by recombinant DNA technology. It has a relatively long half-life and can be delivered in a single bolus instead of requiring an hour-long infusion, as is the case with alteplase.

The phase 3 noninferiority Tenecteplase Reperfusion Therapy in Acute ischemic Cerebrovascular Events (TRACE-2) trial ― the first of its kind in an Asian population ― included 1430 adult ischemic stroke patients at 53 Chinese centers. Patients had to have a National Institutes of Health Stroke Scale (NIHSS) score of 5 to 25 and either not be eligible for or to have refused endovascular therapy.

The mean age of study participants was about 66 years, and the percentage of women was about 31%. The mean baseline NIHSS score was 7 in both groups, and the symptom-onset-to-needle time was similar at 180 minutes for the tenecteplase group and 178.5 minutes for the alteplase group.

Researchers randomly assigned patients to receive tenecteplase or alteplase within 4.5 hours of symptom onset.

Those in the tenecteplase group received 0.25 mg/kg of the drug in a single IV bolus (maximum dose, 25 mg). Control group members who were treated with alteplase were given the drug as a 10% bolus, with the remainder given as a 1-hour infusion (0.9 mg/kg with a maximum dose of 90 mg).

Showed Noninferiority

The primary efficacy outcome was a Modified Rankin Scale (mRS) score of 0–1 at 90 days, which is considered excellent function. About 62% of tenecteplase patients and 58% of alteplase patients attained this outcome (risk ratio, 1.09, 95% CI, 1.00 – 1.18).

The P value was .001 for noninferiority and .06 for superiority, but Li explained that these values may change when considering the site effect.

There were no statistically significant differences between the two drugs on secondary outcomes of favorable function. For example, 73% of tenecteplase patients and 72% of alteplase patients had an mRS score of 0–2 at 3 months, and 50% in the tenecteplase and 49% in the alteplase group improved by 4 or more points on the NIHSS, or had a score of 1 or less, at 24 hours.

The groups also had comparable scores on the European quality-of-life visual analogue scale and on the Barthel index, which measures functional independence related to personal care and mobility.

Tenecteplase also turned out to be as safe at alteplase. About 2% in both groups had symptomatic intracranial hemorrhage within 36 hours, and both groups had that same percentages for such hemorrhages within 90 days. As well, the groups had a similar rate of any intracranial hemorrhage within 90 days (6% and 7%).

The mortality rate was 7% in the tenecteplase group, compared to 5% in the alteplase group.

Adverse events (AEs) occurred in 86% and 87%, and serious AEs in 16% and 15%, of the tenecteplase and alteplase groups, respectively, again with no statistically significant differences.

The research team aims to test the effectiveness of tenecteplase in other stroke patients, including those with minor strokes, those receiving thrombolysis in a later window, and those receiving endovascular therapy, said Li.

Strong Evidence

Commenting on the study for Medscape Medical News, Larry B Goldstein, MD, professor and chair of neurology, University of Kentucky, Lexington, said it’s important to determine the efficacy of tenecteplase among Asians, as they represent “an entirely different population” with unique concerns, such as bleeding complications from anticoagulants.

He noted an advantage of tenecteplase is ease of administration. “You don’t have to go through the loading dose and then the 1-hour infusion,” which poses an “additional hassle” when transferring patients between institutions, he said.

However, he noted that a possible “downside” to having both drugs available in the emergency department is “using the wrong drug at the wrong dose” because of their similar sounding names.

Also commenting on the study, Tudor G. Jovin MD, professor and chair, Department of Neurology, Cooper Medical School of Rowan University, said he welcomes another trial that confirms that these two drugs are biologically similar.

“I’m very glad this trial was done because it adds another very strong piece of evidence of equivalency.”

But the two drugs are not the same in some important respects, said Jovin whose center switched to using tenecteplase almost 3 years ago. That switch has resulted in cutting 17 minutes from the door-to-needle time “which is quite significant,” he said.

“There’s no question that once we used tenecteplase in lieu of tPA, it’s been just so much easier to administer and affects the inter-hospital transfer protocols, because you’re not transferring the patient with a critical care IV. It’s a win-win situation for everyone.”

The study received funding from the National Science and Technology Major Project, the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou). Li, Goldstein, and Jovin report no relevant financial relationships.

International Stroke Conference (ISC) 2023. Late-breaking abstract 5. Presented February 9, 2023.

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