Intra-Arterial Tenecteplase Following Successful Thrombectomy Improves Changes of Excellent Neurological Outcomes in LVO Stroke

Xiaochuan Huo, MD, PhD

Late-breaking data from the ANGEL-TNK trial (NCT05624190) presented at the 2025 International Stroke Conference (ISC), held February 5-7, in Los Angeles, California, showed that the use of intra-arterial Tenecteplase after successful endovascular thrombectomy may improve the likelihood of excellent neurological outcomes among patients with acute large vessel occlusion (LVO) treated between 4.5 to 24 hours.¹

The trial featured 255 participants with clot-caused stroke obstructing a large artery in the brain’s anterior circulation from 19 centers in 13 provinces of China. Following successful restoration of blood flow, patients were then randomized 1:1 to either standard medical care (n = 129) or clot-dissolving tenecteplase infused into the artery near the clot (n = 127). Presented by Xiaochuan Huo, MD, PhD, director of the Neurological Disease Center at Beijing Anzhen Hospital, China, the study used modified Rankin Scale (mRS) scores of 0-1, considered excellent outcome, as the primary efficacy end point.

At 90 days, 40.5% (n = 51) of patients in the intra-arterial Tenecteplase group demonstrated excellent outcome whereas only 26.4% (n = 34) in the medical management group experienced the same (treatment effect, 1.44; 95% CI, 1.06-1.95; P = .02). Mortality was relatively unchanged, as 21.4% (n = 27) of those in the intra-arterial group and 21.7% (n = 28) in the medical management group died during the 90-day period (treatment effect, 0.99; 95% CI, 0.62-1.58; P = .39).

"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," Huo said in a statement. "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."

In the trial, investigators excluded those with intravenous clot-busting drugs or medications that attenuate blood clotting, such as heparin and anti-platelet drugs, during their endovascular procedures. Additional data from the study showed a similar rate of brain bleeds in the 2 days after treatment, regardless of whether patients were on tenecteplase (5.6%) or standard medical care (6.2%)(treatment effect, 0.95; 95% CI, 0.36-2.53; P = .92).

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To be included in this study, patients had to be 18 years of age or older with a National Institutes of Health Stroke Scale (NIHSS) score of at least 2 and symptom onset 4.5-24 hours before basleine CT imaging, including wake-up and unwitnessed strokes. Neuroimaging criteria required a CTA/MRA-confirmed intracranial artery occlusion, an ASPECTS score of at least 6, and specific perfusion thresholds (ischemic core <70 mL, mismatch ratio ≥1.2, mismatch volume ≥15 mL). Eligibility also extended to patients achieving an eTICI score 2b50-3 post-thrombectomy or during diagnostic angiography.²

ANGEL-TNK excluded patients with contraindications to thrombolysis, the need for antiplatelet or anticoagulant therapy within 24 hours post-procedure, or significant comorbidities, including pregnancy, brain tumors, renal failure, or coagulation disorders. Imaging exclusions included midline shift, mass effect, intracranial hemorrhage, acute bilateral strokes, or extracranial artery issues. Other exclusions involved hemodialysis, recent major surgery or bleeding, uncontrolled hypertension (SBP >185 mmHg or DBP >110 mmHg), and any condition or trial participation that could confound the study or increase patient risk.

During the meeting, Huo sat down with NeurologyLive® to discuss the need to compare intra-arterial tenecteplase with standard intravenous thrombolysis in terms of safety and efficacy across diverse patient populations. He emphasized refining patient selection criteria to enhance its applicability and optimizing dosage and delivery techniques to improve outcomes. Huo noted that the ANGEL-TNK study offers a solid foundation for ongoing research to advance this treatment approach.

REFERENCES
1. Removing large brain artery clot, chased with clot-buster shot may improve stroke outcomes. News release. American Stroke Association. February 7, 2025. Accessed February 21, 2025. https://newsroom.heart.org/news/removing-large-brain-artery-clot-chased-with-clot-buster-shot-may-improve-stroke-outcomes
2. Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization (ANGEL-TNK). Clinicaltrials.gov. Updated March 19, 2024. Accessed February 21, 2025. https://clinicaltrials.gov/study/NCT05624190