NCT05624190

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
256

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Feb 2023

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 14, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

November 22, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

February 16, 2023

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2024

Completed
Last Updated

March 19, 2024

Status Verified

March 1, 2024

Enrollment Period

1.4 years

First QC Date

November 14, 2022

Last Update Submit

March 18, 2024

Conditions

Ischemic Stroke, Acute

Outcome Measures

Primary Outcomes (1)

  • Rate of excellent outcome

    Rate of 90 (±7) day modified Rankin scale (mRS) 0-1

    90±7 days after randomization

Secondary Outcomes (10)

  • Rate of sICH (Heidelberg Bleeding Classification)

    within 48 hours after randomization

  • Volume of Tmax>6s

    24 hours (±12 hours) after randomization

  • Infarct core volume change from baseline

    7 days (±1 day) after randomization/at discharge or at 36 hours (±12 hours) after randomization

  • mRS (shift analysis)

    90 days (±7 days) after randomization

  • Rate of good outcome

    90 days (±7 days) after randomization

  • +5 more secondary outcomes

Study Arms (2)

TNK group

EXPERIMENTAL

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

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

control group

ACTIVE COMPARATOR

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

Other: Best Medical Management

Interventions

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

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

Also known as: IA rhTNK-tPA
TNK group
Best Medical ManagementOTHER

Best Medical Management

TNK groupcontrol group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \>18 years;
  • NIHSS ≥2;
  • 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);
  • Pre-stroke mRS score 0-1;
  • Signed informed consent from patient or their health care proxy.
  • CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA;
  • ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI;
  • CT perfusion or MR perfusion: ischemic infarct core \<70ml, mismatch ratio≥1.2, mismatch volume ≥15ml;
  • 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.

You may not qualify if:

  • IV thrombolysis used on admission;
  • Contraindications to intravenous thrombolysis;
  • Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h;
  • IV heparin (heparinized saline allowed);
  • Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;
  • Brain tumor (with mass effect);
  • Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
  • Known coagulopathy, INR\>1.7 or use of novel anticoagulants \< 48h from symptom onset
  • Platelets \< 50\*109/L;
  • Suspicion of septic emboli or endocarditis
  • Renal Failure as defined by a serum creatinine \> 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate \[GFR\] \< 30ml/min;
  • Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason;
  • Suspicion of aortic dissection;
  • Parenchymal organ surgery and biopsy were performed in the past one month;
  • Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month;
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Related Publications (2)

  • 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.

    PMID: 40616323DERIVED

  • 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.

    PMID: 39357896DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Central Study Contacts

Xiaochuan Huo, Dr.

CONTACT

+8613716292262huoxiaochuan@126.com

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Department of interventional neurology

Study Record Dates

First Submitted

November 14, 2022

First Posted

November 22, 2022

Study Start

February 16, 2023

Primary Completion

July 1, 2024

Study Completion

July 1, 2024

Last Updated

March 19, 2024

Record last verified: 2024-03

Data Sharing

IPD Sharing
Will share

Locations

CN(1)