Clinical trial NCT05624190: Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization
Official title: Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator rhTNK-tPA) Thrombolysis for Acute Large Vessel Occlusion After Successful Mechanical Thrombectomy Recanalization -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial (ANGEL-TNK)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Ischemic Stroke, Acute
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2022-11-22
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of excellent outcome
timeFrame: 90±7 days after randomization
Secondary outcomes:
measure: Rate of sICH (Heidelberg Bleeding Classification)
timeFrame: within 48 hours after randomization
measure: Volume of Tmax>6s
timeFrame: 24 hours (±12 hours) after randomization
measure: Infarct core volume change from baseline
timeFrame: 7 days (±1 day) after randomization/at discharge or at 36 hours (±12 hours) after randomization
measure: mRS (shift analysis)
timeFrame: 90 days (±7 days) after randomization
measure: Rate of good outcome
timeFrame: 90 days (±7 days) after randomization
measure: Rate of mRS 0-3
timeFrame: 90 days (±7 days) after randomization
measure: NIHSS 0-1 or decrease ≥10 from baseline NIHSS
timeFrame: 36 hours (±12hours) after randomization
measure: EQ-5D-5L score
timeFrame: 90 days (±7 days) after randomization
measure: All-caused mortality
timeFrame: 90 days (±7 days) after randomization
measure: Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
timeFrame: within 48 hours after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
References: