RecruitingPhase 3NCT07357987

Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke

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

Sponsor

Beijing Tiantan Hospital

Enrollment

488 participants

Start Date

Jan 22, 2026

Study Type

INTERVENTIONAL

Conditions

Ischemic Stroke Medium Vessel Occlusion Endovascular Treatment Tenecteplase

Summary

The ANGEL-MeVO-TNK is a multicentered, prospective, randomized, open label, blinded endpoint (PROBE) phase III trial. A total of 488 AIS patients (age ≥18 years) with acute MeVO-AIS (occlusion of the M2/M3, the A1/A2/A3, the P1/P2/P3, and with baseline NIHSS score \>5 or disabling stroke with NIHSS score 3-5 \[such as neurological deficits in motor strength, language, vision, etc\]), will be enrolled. Patients fulfilling all the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into the IA TNK group or the control group after offering informed content. * The IA TNK group：1) If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) . 2\) If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes. * The control group will be given standard medical management. The study consists of four visits including the day of randomization, 48±12 hours after randomization, and 90±7 days after randomization. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program. The primary outcome is the modified Rankin Scale (mRS) score of 0 to 1 at 90±7 days after onset. The primary safety outcome is the incidence of sICH within 48±12 hours after randomization (ECASS III).

Eligibility

Min Age: 18 Years

Inclusion Criteria7

Age ≥18 years;
Pre-stroke mRS 0-1;
Within 24 h from symptom onset;
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);
Informed consent obtained from patients or their legal representatives.
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;
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 Criteria14

Acute intracranial hemorrhage;
ASPECT ≤5;
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;
Contraindication to TNK;
Known severe allergy to contrast agents (excluding mild rash-type allergic reactions);
Use of heparin or novel oral anticoagulants within the previous 48 hours with an INR ≥ 1.7;
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.;
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);
Acute renal failure, current dialysis, or estimated glomerular filtration rate (eGFR)<30ml/min/1.72m2, and/or serum creatinine>220mmol/L (2.5mg/dl);
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;
Severe non-cardiovascular comorbidity with an expected life expectancy of less than 3 months (e.g., malignant tumors);
Known pregnancy or breastfeeding, or a positive pregnancy test prior to randomization;
Current participation in another drug or device clinical trial;
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).

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Interventions

PROCEDUREIntra-arterial Tenecteplase

1. If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) . 2. If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes.

DRUGstandard medical management

Patients will receive standard medical management as recommended by current guidelines# #《Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)》and《Chinese Guidelines for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack (2022)》