Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke

NCT04733742 | Completed Phase 2 DMC

• 1 other identifier: BRIDGE-TNK
• Study Type: interventional
• Target: 550
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this trial is to investigate whether intravenous rhTNK-tPA prior to endovascular treatment can improve 90-day functional outcome of stroke patients with large vessel occlusion who are thrombolysis-eligible within 4.5 hours of symptom onset.

Conditions

Stroke, Acute; Stroke, Ischemic

Keywords

Thrombolysis; Endovascular treatment; rhTNK-tPA

Outcome Measures

Primary Outcomes (1)

• Proportion of patients functionally independent (mRS score 0 to 2) at 90 days

  functional independence

  90 days

Secondary Outcomes (14)

• Substantial reperfusion at initial angiogram

  within 5 minutes at initial angiogram

• Successful reperfusion at end-of-procedure angiography

  15 minutes after initial angiogram

• First-pass reperfusion

  After artery puncture, but before thrombectomy

• Modified first-pass reperfusion

  After artery puncture, but before thrombectomy

• National Institutes of Health Stroke Scale (NIHSS) score

  5 to 7 days or discharge

Study Arms (2)

Conbined treatment group

EXPERIMENTAL

intravenous tenecteplase bridging with endovascular treatment

Drug: rhTNK-tPA; Other: Endovascular treatment

Endovascular treatment alone group

ACTIVE COMPARATOR

endovascular treatment alone

Other: Endovascular treatment

Interventions

rhTNK-tPA DRUG

intravenous thrombolysis with rhTNK-tPA followed by endovascular treatment

Also known as: TNKase, TNK-tPA

Conbined treatment group

Endovascular treatment OTHER

endovascular treatment

Also known as: intra-arterial treatment, interventional therapy

Conbined treatment group; Endovascular treatment alone group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older;
• Patient with acute ischemic stroke who is eligible for intravenous thrombolysis treatment within 4.5 hours of time last known well;
• No significant prestroke functional disability: for age \<80 years, prestroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;
• MCA-M1 or -M2, basilar artery, or posterior cerebral artery-P1 occlusion proved by CTA/MRA;
• EVT is planned by clinical care team;
• Written informed consent is obtained from patients and/or their legal representatives.

You may not qualify if:

• Intracranial hemorrhage on baseline CT or MR
• Contraindication to intravenous thrombolytics
• Already received intravenous thrombolytic after index stroke
• Known pregnancy, or breastfeeding, or serum beta human chorionic gonadotropin test is positive on admission
• Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys
• Current participation in another investigational drug clinical trial
• Arterial tortuosity and/or other arterial disease that would lead to unstable access platform or prevent the thrombectomy device from reaching the target vessel
• Patient with a preexisting neurological or psychiatric disease that would confound the outcome assessments
• Patient with occlusions in two or more vascular territories (e.g. bilateral territories, or anterior and posterior circulation)
• Mass effect or intracranial neoplasm on baseline CT or MR (except small meningioma)
• Intracranial arteriovenous malformation or aneurysm on baseline CT or MR angiography
• Any terminal disease with a life expectancy less than half a year
• Unlikely to be available for follow-up at 90 days.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead
• CSPC RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD: collaborator

Study Sites (6)

Xinqiao Hospital of Army Medical University

Chongqing, Chongqing Municipality, 400037, China

Location

The Second Hospital of Jiaozuo

Jiaozuo, Henan, China

Location

Wuhan No. 1 Hospital

Wuhan, Hubei, 430000, China

Location

The First Affiliated Hospital, Hengyang Medical School, University of South China

Hengyang, Hunan, China

Location

Xiangtan Central Hospital

Xiangtan, Hunan, 525000, China

Location

The 904th Hospital of CPLA

Wuxi, Jiangsu, 214000, China

Location

Related Publications (6)

• Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Zhao H, Alemseged F, Ng F, Bailey P, Rice H, de Villiers L, Dewey HM, Choi PMC, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Kraemer T, Krause M, Cordato D, Field D, Ma H, O'Brien B, Clissold B, Miteff F, Clissold A, Cloud GC, Bolitho LE, Bonavia L, Bhattacharya A, Wright A, Mamun A, O'Rourke F, Worthington J, Wong AA, Levi CR, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Part 2 investigators. Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1257-1265. doi: 10.1001/jama.2020.1511.

  PMID: 32078683 BACKGROUND

• Mai LM, Oczkowski W. Tenecteplase before thrombectomy for ischemic stroke improved reperfusion compared with alteplase. Ann Intern Med. 2018 Aug 21;169(4):JC20. doi: 10.7326/ACPJC-2018-169-4-020. No abstract available.

  PMID: 30128510 BACKGROUND

• Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405.

  PMID: 29694815 BACKGROUND

• Zi W, Qiu Z, Li F, Sang H, Wu D, Luo W, Liu S, Yuan J, Song J, Shi Z, Huang W, Zhang M, Liu W, Guo Z, Qiu T, Shi Q, Zhou P, Wang L, Fu X, Liu S, Yang S, Zhang S, Zhou Z, Huang X, Wang Y, Luo J, Bai Y, Zhang M, Wu Y, Zeng G, Wan Y, Wen C, Wen H, Ling W, Chen Z, Peng M, Ai Z, Guo F, Li H, Guo J, Guan H, Wang Z, Liu Y, Pu J, Wang Z, Liu H, Chen L, Huang J, Yang G, Gong Z, Shuai J, Nogueira RG, Yang Q; DEVT Trial Investigators. Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial. JAMA. 2021 Jan 19;325(3):234-243. doi: 10.1001/jama.2020.23523.

  PMID: 33464335 RESULT

• Qiu Z, Li F, Sang H, Yuan G, Xie D, Zhou K, Li M, Meng Z, Kong Z, Ruan Z, Li C, Yang G, Wu J, Long C, Yang B, Hu H, Li Y, Luo J, Shi Z, Huang X, Jiang S, Yi T, Zeng G, Liu J, Luo X, Liu S, Chang M, Wu Y, Tang Y, Tian Z, Yan Z, Zhao H, Peng Y, Dai H, Zhou P, Li H, Liu W, Song D, Lei B, Xia Z, Tan X, Zhao M, Feng X, Cai L, Li Q, Wu Y, Jiang B, Tian Y, Li L, Jiang L, Long X, You F, Tao J, Zhou J, Wu D, Zheng C, Yin C, Wang D, Lu M, Albers GW, Nogueira RG, Campbell BCV, Nguyen TN, Saver JL, Zi W, Yang Q; BRIDGE-TNK Trial Investigators. Intravenous Tenecteplase before Thrombectomy in Stroke. N Engl J Med. 2025 Jul 10;393(2):139-150. doi: 10.1056/NEJMoa2503867. Epub 2025 May 21.

  PMID: 40396577 DERIVED

• Qiu Z, Li F, Xie D, Yuan G, Nguyen TN, Zhou K, Nogueira RG, Saver JL, Campbell BCV, Albers GW, Sang H, Li L, Tian Y, Meng Z, Wang D, Zi W, Yang Q; BRIDGE-TNK investigators. Efficacy and Safety of Intravenous Tenecteplase Before Endovascular Thrombectomy for Acute Ischemic Stroke: The Multicenter, Randomized, BRIDGE-TNK Trial Protocol. J Am Heart Assoc. 2024 Nov 5;13(21):e036765. doi: 10.1161/JAHA.124.036765. Epub 2024 Oct 22.

  PMID: 39435713 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Interventions

Tenecteplase; TNK-tissue plasminogen activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Qingwu Yang, MD

  Neurology, Xinqiao Hospital of the Army Medical University

  PRINCIPAL INVESTIGATOR

• Raul G Nogueira, MD

  Marcus Stroke & Neuroscience Center, Grady Memorial Hospital, Emory University, Atlanta, USA

  PRINCIPAL INVESTIGATOR

• Jeffrey L Saver, MD

  Neurology, University of California, Los Angeles, USA

  PRINCIPAL INVESTIGATOR

• Wenjie Zi, MD

  Neurology, Xinqiao Hospital of the Army Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: February 2, 2021
• Study Start: May 9, 2022
• Primary Completion: December 16, 2024
• Study Completion: February 7, 2025
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Related papers published 3 months later, the IPD will be shared.
• Access Criteria: yangqwmlys@163.com ziwenjie1981@163.com

Locations

CN (6)