Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke (ANGEL-MeVO-TNK)

Capital Medical University

Status and phase: Not yet enrolling; Phase 3

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

Treatments: Drug: standard medical management; Procedure: Intra-arterial Tenecteplase

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07357987

ANGEL-MeVO-TNK

Details and patient eligibility

About

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 will receive IA TNK (0.2-0.3 mg/min, for 15 -30min), be infused slowly.
• 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).

Enrollment: 488 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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488 participants in 2 patient groups

IA TNK group

Experimental group

Description:

During thrombolysis, once vessel recanalization is achieved, immediate termination of the infusion is recommended. If thrombus migration, residual distal embolization, or other situations occur during drug administration, the operator may decide whether to continue treatment at their discretion. Otherwise, TNK will be administered at the specified dose and infusion rate and repeat angiography will be performed after 15 or 30 minutes, followed by termination of the procedure. After completion of the procedure, patients will receive standard medical management as recommended by current guidelines#

Treatment:

Procedure: Intra-arterial Tenecteplase

Control group (Standard medical management group)

Active Comparator group

Description:

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)》

Treatment:

Drug: standard medical management