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

NCT ID: NCT05624190

Last Updated: 2024-03-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 256 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-16
• Study Completion Date: 2024-07-31

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.

Conditions

Ischemic Stroke, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

TNK group

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

The administration of rhTNK-tPA will be infused constant and slowly over 15min (0.125 mg/kg, Max 12.5mg) through a microcatheter.

Best Medical Management

Intervention Type: OTHER

Best Medical Management

control group

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

Group Type: ACTIVE_COMPARATOR

Best Medical Management

Intervention Type: OTHER

Best Medical Management

Interventions

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

The administration of rhTNK-tPA will be infused constant and slowly over 15min (0.125 mg/kg, Max 12.5mg) through a microcatheter.

Intervention Type: DRUG

Best Medical Management

Best Medical Management

Intervention Type: OTHER

Other Intervention Names

IA rhTNK-tPA

Eligibility Criteria

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.

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

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).

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhongrong Miao

Director of Department of interventional neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaochuan Huo, Dr.

Role: CONTACT

huoxiaochuan@126.com

+8613716292262

Facility Contacts

Zhongrong Miao

Role: primary

References

Miao Z, Luo G, Song L, Sun D, Chen W, Yao X, Pan Y, Liu Y, Yuan G, Wen C, Wei M, Cai X, Yang Q, Zhou Z, Chang M, Nan G, Wang J, Xiang G, Zhou L, Gao W, Zhang H, Hao J, Xu C, Sun Y, Yi T, Feng G, Han H, Gao F, Ma N, Mo D, Sun X, Deng Y, Tong X, Li X, Jia B, Wang B, He Z, Yang M, Zhao X, Zhang X, Zhang L, Li S, Tong X, Jing J, Xiong Y, Liu T, Li Z, Ren Z, Wang Y, Liebeskind DS, Jovin TG, Nguyen TN, Wang Y, Liu L, Yan B, Huo X; ANGEL-TNK Investigators. Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy: The ANGEL-TNK Randomized Clinical Trial. JAMA. 2025 Aug 19;334(7):582-591. doi: 10.1001/jama.2025.10800.

Reference Type: DERIVED

PMID: 40616323 (View on PubMed)

Huo X, Luo G, Sun D, Nguyen T, Abdalkader M, Chen W, Yao X, Yuan G, Yi T, Han H, Pan Y, Jovin TG, Liebeskind DS, Liu L, Zhao X, Ren Z, Wang Y, Wang Y, Yan B, Miao Z. Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial. Stroke Vasc Neurol. 2025 Aug 26;10(4):508-513. doi: 10.1136/svn-2024-003318.

Reference Type: DERIVED

PMID: 39357896 (View on PubMed)

Other Identifiers

HX-A-2022041

Identifier Type: -

Identifier Source: org_study_id