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

Phase 4

Recruiting

• Conditions: Ischemic Stroke, Acute
• Interventions: Drug: Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA); Other: Best Medical Management

• Registration Number: NCT05624190
• Lead Sponsor: Beijing Tiantan Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-14
• Study First Submitted QC: 2022-11-21
• Study First Posted: 2022-11-22
• Study Start: 2023-02-16
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-18
• Last Update Posted: 2024-03-19
• Primary Completion: 2024-07
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 256

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TNK group	Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)	Patients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization
control group	Best Medical Management	Patients of this group will receive Best Medical Management (BMM) alone after successful mechanical thrombectomy (MT) recanalization
TNK group	Best Medical Management	Patients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization

Primary Outcome Measures

Name	Time	Method
Rate of excellent outcome	90±7 days after randomization	Rate of 90 (±7) day modified Rankin scale (mRS) 0-1

Secondary Outcome Measures

Name	Time	Method
Infarct core volume change from baseline	7 days (±1 day) after randomization/at discharge or at 36 hours (±12 hours) after randomization	Infarct core volume change from baseline, assessed with NCCT at 7 days (±1 day) after randomization/at discharge or with MRI at 36 hours (±12 hours)
mRS (shift analysis)	90 days (±7 days) after randomization	mRS (shift analysis)
All-caused mortality	90 days (±7 days) after randomization	All-caused mortality
Rate of sICH (Heidelberg Bleeding Classification)	within 48 hours after randomization	Rate of sICH (Heidelberg Bleeding Classification)
Rate of good outcome	90 days (±7 days) after randomization	Rate of mRS 0-2
NIHSS 0-1 or decrease ≥10 from baseline NIHSS	36 hours (±12hours) after randomization	NIHSS 0-1 or decrease ≥10 from baseline NIHSS
EQ-5D-5L score	90 days (±7 days) after randomization	EQ-5D-5L score
Rate of mRS 0-3	90 days (±7 days) after randomization	Rate of mRS 0-3
Volume of Tmax>6s	24 hours (±12 hours) after randomization
Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)	within 48 hours after randomization	Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)

Trial Locations

Locations (1)

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China