Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization (ANGEL-TNK)

Capital Medical University

Status and phase: Enrolling; Phase 4

Conditions: Ischemic Stroke, Acute

Treatments: Other: Best Medical Management; Drug: Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)

Study type: Interventional

Funder types: Other

Identifiers

NCT05624190

HX-A-2022041

Details and patient eligibility

About

The goal of this clinical trial is to evaluate whether intra-arterial (IA) rhTNK-tPA thrombolysis can improve neurological outcomes in acute large vessel occlusion patients after successful mechanical thrombectomy (MT) recanalization between 4.5- 24 hours from symptom onset. Participants enrolled will be randomly assigned to study or control arm with a 1:1ratio. Study group will receive IA rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus best medical management, and control receive best medical management alone.

Enrollment: 256 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Clinical Inclusion Criteria:

1. Age >18 years;
2. NIHSS ≥2;
3. Onset of symptoms to baseline CT imaging time: 4.5 to 24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW);
4. Pre-stroke mRS score 0-1;
5. Signed informed consent from patient or their health care proxy.

Neuroimaging Inclusion Criteria:

1. CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA;
2. ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI;
3. CT perfusion or MR perfusion: ischemic infarct core <70ml, mismatch ratio≥1.2, mismatch volume ≥15ml;
4. Treated with MT resulting in an eTICI score 2b50-3 at end of the procedure. Patients with an eTICI score 2b50-3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.

Exclusion criteria

Clinical Exclusion Criteria:

1. IV thrombolysis used on admission;
2. Contraindications to intravenous thrombolysis;
3. Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h;
4. IV heparin (heparinized saline allowed);
5. Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;
6. Brain tumor (with mass effect);
7. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
8. Known coagulopathy, INR>1.7 or use of novel anticoagulants < 48h from symptom onset
9. Platelets < 50*109/L;
10. Suspicion of septic emboli or endocarditis
11. Renal Failure as defined by a serum creatinine > 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate [GFR] < 30ml/min;
12. Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason;
13. Suspicion of aortic dissection;
14. Parenchymal organ surgery and biopsy were performed in the past one month;
15. Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month;
16. History of life-threatening allergy (more than rash) to contrast medium;
17. SBP >185 mmHg or DBP >110 mmHg refractory to treatment;
18. Serious, advanced, terminal illness with anticipated life expectancy < 6 months;
19. Participation in another randomized clinical trial that could confound the evaluation of the study;
20. Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients (e.g. inability to understand and/or comply with study procedures and/or follow-up due to mental disorders, cognitive or mood disorders).

Specific Neuroimaging Exclusion Criteria

1. Midline shift or herniation, mass effect with effacement of the ventricles
2. Evidence of acute intracranial hemorrhage on CT/MRI
3. Acute bilateral strokes or multiple intracranial vessel occlusions
4. Isolated extracranial ICA occlusion or tandem carotid / MCA occlusion
5. Dissection of occluded artery on DSA after thrombectomy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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256 participants in 2 patient groups

TNK group

Experimental group

Description:

Patients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization

Treatment:

Drug: Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)

Other: Best Medical Management

control group

Active Comparator group

Description:

Patients of this group will receive Best Medical Management (BMM) alone after successful mechanical thrombectomy (MT) recanalization

Treatment:

Other: Best Medical Management