Tenecteplase injection after clot removal improves stroke recovery

Removing a blood clot from a large brain artery, then injecting the clot-dissolving drug tenecteplase into the artery resulted in stroke survivors being more likely to have better function 90 days after their stroke than those receiving standard clot removal, according to preliminary late-breaking science presented today at the American Stroke Association's International Stroke Conference 2025. The conference, in Los Angeles, Feb. 5-7, 2025, is a world premier meeting for researchers and clinicians dedicated to the science of stroke and brain health.

About 1 in 5 clot-caused (ischemic) strokes result from a clot obstructing a large artery (large vessel occlusions) in the brain. The standard of care in the U.S. per the American Heart Association/American Stroke Association 2019 Guidelines for the Early Management of Patients with Acute Ischemic Stroke and in China for this type of stroke is prompt removal of the clot to restore blood flow using minimally invasive endovascular treatment – a procedure that inserts a slim catheter (small tube) and/or a stent into an artery to retrieve the clot and restore blood flow, preventing further brain damage.

Without treatment, more than 80% of people with strokes caused by large vessel occlusions are disabled, and 20% die, based on prior studies. Even when clots are successfully removed, up to half of the people may die or be disabled three months later.

Endovascular treatment can help restore blood flow in a blocked large blood vessel. However, it might not improve blood flow in the smaller vessels and microcirculation in the area. This clinical trial tests whether delivering tenecteplase directly into the affected artery after endovascular treatment can break up blood clots in the small vessels and improve blood flow, reducing the amount of brain tissue that lacks blood supply."

Xiaochuan Huo, M.D., Ph.D., lead author of the study and director of the neurological disease center at Beijing Anzhen Hospital, China

The current study, conducted at 19 centers in China, evaluated the safety and effectiveness of injecting tenecteplase directly into a large brain artery (intra-arterial injection) near where a clot was removed and restoring blood flow. All participants had large vessel occlusions and were treated between 4.5 hours and 24 hours after the last time they were observed to be well. According to the study protocols, 127 patients received tenecteplase and successfully underwent endovascular therapy, and 129 received standard medical care (in the full analysis population for the final results) after successful endovascular therapy. Disability was measured by a score of 0-1 on the modified Rankin Scale with ratings from 0 (no disability) to 6 (death).

The analysis found:

• Stroke survivors were 44% more likely to have an excellent outcome (modified Rankin score 0-1) after 90 days if they received the tenecteplase injection and standard care after clot removal compared to those who received only standard care (40.5% vs. 26.4%).
• Rates of brain bleeds in the two days after treatment were similar in those receiving tenecteplase (5.6%) and those receiving standard medical treatment (6.2%).
• Rates of death from any cause within 90 days were similar in those receiving tenecteplase (21.4%) and those receiving standard medical treatment (21.7%).

"Intra-arterial tenecteplase after successful thrombectomy could improve the percentage of people with an excellent outcome. It could also improve the rate of large vessel occlusion stroke survivors who can return to society and live independently," Huo said.

The researchers are following the participants to assess their one-year outcomes. Huo said their results may someday be used to change treatment guidelines for stroke survivors who have undergone successful clot removal. "We still need to directly analyze the individual data of participants in this and other trials – an individual meta-analysis – in order to release a high evidence-based recommendation," Huo said.

The study did not include patients treated with intravenous clot-busting drugs or medications that reduce blood clotting, like heparin and anti-platelet drugs, during their endovascular procedures. This means that the benefits of intra-arterial tenecteplase shown in this study may not apply to people who received those treatments.

Study background, details and design:

• ANGEL-TNK enrolled 255 participants (mean age of 70; 44.7% female) between February 2023 and March 2024 at 19 centers in 13 provinces of China.
• All participants were adults who experienced a clot-caused (ischemic) stroke obstructing a large artery in the brain's anterior circulation. All had blood flow successfully restored by having the clot removed via catheter or aspiration (breaks up and draws the clot through the tube) between 4.5 and 24 hours from the time they were last known to be well. No participants were disabled before their stroke. The main exclusion criterion was treatment with intravenous clot-busting medications (which, by Chinese guidelines, must be used within 4.5 hours after a person was last known to be well).
• After successful restoration of blood flow, participants were randomized to receive either standard medical care or to have the clot-dissolving drug tenecteplase infused into the artery near the clot.
• The primary assessment for the effectiveness of the additional treatment was the percentage of participants who had no symptoms or some symptoms but no disability 90 days later, as measured by a score of 0-1 on the modified Rankin Scale administered and scored by someone without knowledge of the treatment group.
• The primary assessments for safety were brain bleeding within 48 hours of treatment or death from any cause within 90 days.