Loading ...

BASEL, SWITZERLAND — Intravenous (IV) tenecteplase improves functional outcome in patients with stroke presenting beyond 4.5 hours with acute large vessel occlusion (LVO) and salvageable brain tissue identified on perfusion imaging, but without access to endovascular therapy, the results of the TRACE-III trial showed.

"The TRACE-III trial demonstrates a clear benefit of IV tenecteplase in patients with large vessel occlusion and tissue at risk of infarction up to 24 hours after symptom onset. These results are important for patients arriving in the late or unknown time window who do not have access to immediate endovascular thrombectomy," said study investigator Yunyun Xiong, MD, Beijing Tiantan Hospital, Beijing, China.

"The TRACE-III trial was conducted in rural China in patients with large vessel occlusion who didn't have access to thrombectomy. But it is applicable to large parts of the world where thrombectomy is not easily available. I think this trial will make a substantial difference to practice in these areas," study co-author Mark Parsons, MD, University of New South Wales, Sydney, Australia, told Medscape Medical News.

The trial was presented at the European Stroke Organization Conference (ESOC) 2024 annual meeting.

Clear Benefit Up to 24 Hours

Acute LVO accounts for 30%-46% of the ischemic stroke, with a 90-day mortality rate of 60%-80%. Current American Heart Association/American Stroke Association guidelines recommend IV thrombolysis bridging mechanical thrombectomy as the first-line treatment for acute LVO of anterior circulation stroke within 4.5 hours of stroke onset. However, a majority of patients arrive at a hospital outside the 4.5-hour time window.

To date, there are limited data on the efficacy and safety of IV thrombolysis in the later time window. TRACE-III is the first phase 3 trial of tenecteplase with salvageable tissue postischemic stroke due to LVO beyond 4.5 hours.

The investigators enrolled 516 patients with acute ischemic stroke due to LVO in the anterior circulation within 4.5-24 hours of symptom onset or last seen well, had salvageable tissue (ischemic core volume, < 70 mL; mismatch ratio, ≥ 1.8; and mismatch volume, ≥ 15 mL) based on CT perfusion or MRI perfusion-weighted imaging, and were unable to access endovascular thrombectomy. They were randomly assigned to receive IV tenecteplase (0.25 mg/kg bodyweight) or standard medical treatment.

Results showed that treatment with tenecteplase was associated with a higher percentage of patients achieving a favorable outcome (modified Rankin Scale score, 0 or 1) at 90 days than standard medical treatment (33.0% vs 24.2%; relative risk, 1.37; 95% CI, 1.04-1.81; P = .03).

Mortality at 90 days was comparable between groups. There was a numerically higher rate of symptomatic intracranial hemorrhage in the tenecteplase group (3.0% vs 0.8%).

Selecting the Right Patients

It is essential to select patients that might benefit from thrombolysis in this late-presenting cohort with advanced imaging, said Parsons.

"It is important to exclude patients in the late time window who already have significant areas of ischemic brain, as thrombolysis can be harmful in these patients, and it is not possible to assess this properly without perfusion imaging," he added.

In high-income countries such as Western Europe, the United States, and Australia, the time window has been extended to 24 hours for thrombectomy on the basis of advanced imaging modalities, and patients have the opportunity to receive thrombectomy outside the IV thrombolysis time window.

However, for many patients in low-income or middle-income countries, thrombectomy is not an option due to the financial burden and the lack of routinely available advanced perfusion imaging and automated software for interpretation.

"This will mean that these rural centers, where it may not be possible to get patients to a thrombectomy center in time for endovascular therapy, will have to take up perfusion imaging."

Parsons added that most contemporary CT scanners can now do perfusion imaging. "The expensive part has been the perfusion analysis software. But there are new software packages now being introduced that are less expensive."

He pointed out that a recent US trial (TIMELESS) tested a similar strategy of tenecteplase in patients with LVO stroke arriving after 4.5 hours.

TIMELESS failed to show a benefit of thrombolysis, but that may have been because that trial was conducted in comprehensive stroke centers and patients went on to receive thrombectomy soon after thrombolysis was given, Parsons suggested.

Commenting on the TRACE-III trial, Simona Sacco, MD, University of L'Aquila, L'Aquila, Italy, said, it was a "very interesting and important trial which addresses a particular population of patients — those with large vessel occlusion but with no access to thrombectomy. This is a large patient group with an unmet need. The results show we can now really do something for these patients."

But the TRACE-III trial was performed in a single country in a system, which may be different from other countries, so this probably needs to be replicated in other parts of the world, cautioned Sacco, who is also president-elect of the European Stroke Organisation and editor-in-chief of the journal Cephalalgia.

The TRACE-III trial was funded by the National Natural Science Foundation of China, Beijing Municipal Science & Technology Commission, and Beijing Hospitals Authority. Tenecteplase was provided by Guangzhou Recomgen Biotech. The study authors reported no relevant disclosures.

Sacco reported grants for research from Novartis and Uriach and consulting fees from Novartis, Allergan-AbbVie, Teva, Lilly, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca. She also reported payment for lectures from Novartis, Allergan-AbbVie, Teva, Lundbeck, Pfizer, Novo Nordisk, Abbott, and AstraZeneca and support for attending conferences from Lilly, Novartis, Teva, Lundbeck, and Pfizer.