Tenecteplase delivered into the artery for acute medium-vessel stroke

Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke: the ANGEL-MeVO-TNK Randomized Clinical Trial

This trial will test whether giving tenecteplase directly into the blocked artery helps adults with acute medium-vessel ischemic stroke recover better when treated within 24 hours.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 488 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tiantan Hospital (other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07357987 on ClinicalTrials.gov

What this trial studies

The ANGEL-MeVO-TNK is a multicenter, randomized, open-label, blinded-endpoint phase III trial enrolling 488 adults with acute medium-vessel occlusion ischemic stroke within 24 hours. Participants are randomized 1:1 to intra-arterial tenecteplase given by slow, super-selective infusion during angiography (initial 0.0625 mg/kg over 15 minutes with a possible repeat dose) or to standard medical management. Outcome assessors are blinded to treatment allocation, and key eligibility includes limited infarct size on imaging, pre-stroke functional independence, and a baseline NIHSS indicating moderate or disabling deficits. The trial measures whether intra-arterial tenecteplase improves artery reopening and functional outcomes compared with usual care.

Who should consider this trial

Good fit: Adults (≥18) with a confirmed isolated medium-vessel occlusion (M2/M3, A1–A3, P1–P3), symptom onset within 24 hours, baseline NIHSS >5 (or 3–5 with disabling deficits), pre-stroke mRS 0–1, and infarct volume less than half the artery territory are ideal candidates.

Not a fit: Patients with acute intracranial hemorrhage, very large infarcts (ASPECTS ≤5 or >50% territory), MeVO caused by clot migration from a large-vessel occlusion, or those who already received certain prior recanalization procedures are unlikely to benefit.

Why it matters

Potential benefit: If successful, the approach could increase artery reopening rates and improve functional recovery for patients with medium-vessel occlusion stroke.

How similar studies have performed: Intravenous tenecteplase has shown promise in other stroke studies and small early-phase or observational reports suggest intra-arterial thrombolysis may help, but intra-arterial tenecteplase for MeVO is relatively novel and not yet proven in phase III.

Eligibility criteria

Inclusion Criteria:

Clinical Inclusion Criteria:

1. Age ≥18 years;
2. Pre-stroke mRS 0-1;
3. Within 24 h from symptom onset;
4. Baseline National Institutes of Health Stroke Scale (NIHSS) score \>5 or baseline NIHSS 3-5 with disabling deficit (e.g., loss of hand function, aphasia, hemianopia);
5. Informed consent obtained from patients or their legal representatives.

Imaging Inclusion Criteria:

1. Baseline CTA/MRA/DSA diagnosed isolated MeVO, referring to the M2/M3 segment of the MCA, the A1/A2/A3 segment of the ACA, the P1/P2/P3 segment of the PCA;
2. NCCT or MRI DWI imaging showing that the territory of the ischemic infarct volume is less than 50% of the estimated territory supplied by the occluded artery.

Exclusion Criteria:

1. Acute intracranial hemorrhage;
2. ASPECT ≤5;
3. MeVO secondary to spontaneous fragmentation and distal migration of thrombus from an acute large vessel occlusion, or occurring after intravenous thrombolysis (IVT), intra-arterial thrombolysis, or endovascular thrombectomy;
4. Contraindication to TNK;
5. Known severe allergy to contrast agents (excluding mild rash-type allergic reactions);
6. Use of heparin or novel oral anticoagulants within the previous 48 hours with an INR ≥ 1.7;
7. A history of major bleeding within the past 6 months or the presence of conditions such as active gastrointestinal ulcer, aortic dissection, platelet count \< 100 × 10⁹/L, etc.;
8. Radiologically confirmed vascular malformations, arterial dissection, intracranial aneurysm (diameter≥3 mm), tumors (except small meningiomas), cerebral vasculitis, cerebral amyloid angiopathy, or other major non-ischemic intracranial diseases (e.g., multiple sclerosis);
9. Acute renal failure, current dialysis, or estimated glomerular filtration rate (eGFR)\<30ml/min/1.72m2, and/or serum creatinine\>220mmol/L (2.5mg/dl);
10. History of severe liver disease, or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or glutamyl transferase (GGT) ≥3×upper limit of normal value (ULN) and/or total bilirubin (TBIL) ≥2×ULN;
11. Severe non-cardiovascular comorbidity with an expected life expectancy of less than 3 months (e.g., malignant tumors);
12. Known pregnancy or breastfeeding, or a positive pregnancy test prior to randomization;
13. Current participation in another drug or device clinical trial;
14. Any other condition deemed by the investigator to make the patient unsuitable for participation in the study or to pose a significant risk to the patient (e.g., inability to understand and/or comply with study procedures and/or follow-up due to psychiatric illness, cognitive impairment, or emotional disorders).

Where this trial is running

Beijing, Beijing Municipality

• Beijing Tiantan Hospital, Capital Medical University — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Liping Liu

Conditions: Ischemic Stroke, Medium Vessel Occlusion, Tenecteplase, Endovascular Treatment