Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke (BRIDGE-TNK)

Intravenous rhTNK-tPA Bridging With Endovascular Treatment Versus Endovascular Treatment Alone For Stroke Patient With Large Vessel Occlusion: A Multicenter, Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Ischemic; Stroke, Acute
• Intervention / Treatment: Drug: rhTNK-tPA; Other: Endovascular treatment

Detailed Description

The DEVT, SKIP and DIRECT-MT trials showed that endovascular treatment alone is not inferior to intravenous alteplase bridging with endovascular treatment in terms of achieving 90-day functional independence for stroke patients with large vessel occlusion. The EXTEND-IA TNK part 1 and part 2 demonstrated that intravenous thrombolysis with tenecteplase is superior to alteplase before endovascular treatment. However, it is unclear whether intravenous tenecteplase bridging with endovascular treatment is superior to endovascular treatment alone. The purpose of this trial is to investigate whether intravenous rhTNK-tPA bridging with endovascular treatment is better than endovascular treatment alone for stroke patients with large vessel occlusion who are thrombolysis-eligible within 4.5 hours of onset.

• Study Type: Interventional
• Enrollment (Estimated): 498
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Zhongming Qiu, MD; Phone Number: +8613236599269; Email: qiuzhongmingdoctor@163.com
• Study Contact Backup: Name: Fengli Li, MD; Phone Number: +8617358339092; Email: lifengli01@yeah.net

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Recruiting
      • Xinqiao Hospital of Army Medical University
      • Contact: Wenjie Zi, MD; Phone Number: +8618523033816; Email: ziwenjie1981@163.com
      • Contact: Zhongming Qiu; Phone Number: +8613236599269; Email: qiuzhongmingdoctor@163.com
  • Guangdong
    • Maoming, Guangdong, China, 525000
      • Not yet recruiting
      • Maoming Traditional Chinese Medicine Hospital
      • Contact: Wenguo Huang, MS; Phone Number: 8613929795299; Email: 13929795299@139.com
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Wuhan No. 1 Hospital
      • Contact: Wenhua Liu, MD; Phone Number: 8618871588816; Email: leeoowh@yeah.net
  • Jiangsu
    • Wuxi, Jiangsu, China, 214000
      • Recruiting
      • The 904th Hospital of CPLA
      • Contact: Zhonghua Shi, MD; Phone Number: 8618921150310; Email: 18921150310@189.cn
  • Jilin
    • Changchun, Jilin, China, 130000
      • Not yet recruiting
      • The First Affiliated Hospital of Jilin University
      • Contact: Shouchun Wang, MD; Phone Number: 8613596060906; Email: wangsc13@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 years or older;
2. Acute ischemic stroke confirmed by clinical symptoms or imaging examination;
3. MCA-M1 or -M2, basilar artery, or posterior cerebral artery-P1 occlusion proved by CTA/MRA;
4. Eligible for intravenous thrombolysis with TNK-tPA;
5. Time from stroke onset to randomization within 4.25 hours;
6. Written informed consent is obtained from patients and/or their legal representatives.

Exclusion Criteria:

1. CT or MR evidence of intracranial hemorrhage;
2. Contraindications of intravenous thrombolysis;
3. Currently in pregnant or lactating or serum beta HCG test is positive on admission;
4. Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys;
5. Current participation in another clinical trial
6. Arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel;
7. Patients with a preexisting neurological or psychiatric disease that would confound the neurological functional evaluations;
8. Patients with occlusions in multiple vascular territories (e.g. bilateral anterior circulation, or anterior/posterior circulation);
9. CT or MR evidence of mass effect or intracranial tumor (except small meningioma);
10. CT or MR angiography evidence of intracranial arteriovenous malformations or aneurysms;
11. Any terminal illness with life expectancy less than 6 months;
12. Unlikely to be available for 90-day follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conbined treatment group; intravenous tenecteplase bridging with endovascular treatment	Drug: rhTNK-tPA; intravenous thrombolysis with rhTNK-tPA followed by endovascular treatment; Other Names: TNKase; TNK-tPA; Other: Endovascular treatment; endovascular treatment; Other Names: interventional therapy; intra-arterial treatment
Active Comparator: Endovascular treatment alone group; endovascular treatment alone	Other: Endovascular treatment; endovascular treatment; Other Names: interventional therapy; intra-arterial treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin scale score	disability level	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural-related complications and severe adverse events	evaluate complications and any adverse events	within 90 days
Mortality within 90 days	evaluate death rate of the two treatment groups	90 days
Proportion of patients non-disabled (mRS score 0 to 1) or return to pre-morbid mRS score at 90 days (for patients with mRS > 1)	excellent outcome	90 days
Proportion of patients functionally independent (mRS score 0 to 2) at 90 days	functional independence	90 days
Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3)	ambulatory or bodily needs-capable or better	90 days
Substantial reperfusion at initial angiogram	evaluate effect of tenecteplase on reperfusion	within 5 minutes at initial angiogram
Revascularization rates at 48 hours from randomization	evaluate vascular patency after treatment	at 48 hours from randomization
Early neurologic improvement	Early neurologic improvement was defined as a reduction of 8 points in the NIHSS score between baseline and 72 hours or as a score of 0 or 1 at 72 hours. An 8-point reduction is considered to be highly clinically significant	72 hours
Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L)	Health-related quality of life	90 days
Symptomatic/Asymptomatic intracranial hemorrhage within 48 hours	evaluate intracranial hemorrhage	within 48 hours after endovascular treatment
Parenchymal hematoma	evaluate intracranial hemorrhage	within 48 hours after endovascular treatment

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing
• Collaborators: CSPC RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD
• Investigators: Principal Investigator: Qingwu Yang, MD, Neurology, Xinqiao Hospital of the Army Medical University; Principal Investigator: Wenjie Zi, 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

Publications and helpful links

General Publications

• 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. Erratum In: JAMA. 2022 Mar 8;327(10):985.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 31, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 27, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Thrombolysis; Endovascular treatment; rhTNK-tPA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: BRIDGE-TNK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: study data without patient information
• IPD Sharing Time Frame: Related papers published 3 months later, the IPD will be shared.
• IPD Sharing Access Criteria: yangqwmlys@163.com ziwenjie1981@163.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No