Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke

NCT ID: NCT04733742

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 550 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-09
• Study Completion Date: 2025-02-07

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.

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.

Conditions

Stroke, Acute; Stroke, Ischemic

Study Design

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

Study Groups

Conbined treatment group

intravenous tenecteplase bridging with endovascular treatment

Group Type: EXPERIMENTAL

rhTNK-tPA

Intervention Type: DRUG

intravenous thrombolysis with rhTNK-tPA followed by endovascular treatment

Endovascular treatment

Intervention Type: OTHER

endovascular treatment

Endovascular treatment alone group

endovascular treatment alone

Group Type: ACTIVE_COMPARATOR

Endovascular treatment

Intervention Type: OTHER

endovascular treatment

Interventions

rhTNK-tPA

intravenous thrombolysis with rhTNK-tPA followed by endovascular treatment

Intervention Type: DRUG

Endovascular treatment

endovascular treatment

Intervention Type: OTHER

Other Intervention Names

TNKase; TNK-tPA; intra-arterial treatment; interventional therapy

Eligibility Criteria

Inclusion Criteria

1. Aged 18 years or older;

2. Patient with acute ischemic stroke who is eligible for intravenous thrombolysis treatment within 4.5 hours of time last known well;

3. No significant prestroke functional disability: for age <80 years, prestroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;

4. MCA-M1 or -M2, basilar artery, or posterior cerebral artery-P1 occlusion proved by CTA/MRA;

5. EVT is planned by clinical care team;

6. Written informed consent is obtained from patients and/or their legal representatives.

Exclusion Criteria

1. Intracranial hemorrhage on baseline CT or MR

2. Contraindication to intravenous thrombolytics

3. Already received intravenous thrombolytic after index stroke

4. Known pregnancy, or breastfeeding, or serum beta human chorionic gonadotropin test is positive on admission

5. Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys

6. Current participation in another investigational drug clinical trial

7. Arterial tortuosity and/or other arterial disease that would lead to unstable access platform or prevent the thrombectomy device from reaching the target vessel

8. Patient with a preexisting neurological or psychiatric disease that would confound the outcome assessments

9. Patient with occlusions in two or more vascular territories (e.g. bilateral territories, or anterior and posterior circulation)

10. Mass effect or intracranial neoplasm on baseline CT or MR (except small meningioma)

11. Intracranial arteriovenous malformation or aneurysm on baseline CT or MR angiography

12. Any terminal disease with a life expectancy less than half a year

13. Unlikely to be available for follow-up at 90 days.

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

Sponsors

CSPC RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD

UNKNOWN

Sponsor Role: collaborator

Xinqiao Hospital of Chongqing

OTHER

Sponsor Role: lead

Responsible Party

Zhongming Qiu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qingwu Yang, MD

Role: PRINCIPAL_INVESTIGATOR

Neurology, Xinqiao Hospital of the Army Medical University

Raul G Nogueira, MD

Role: PRINCIPAL_INVESTIGATOR

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

Jeffrey L Saver, MD

Role: PRINCIPAL_INVESTIGATOR

Neurology, University of California, Los Angeles, USA

Wenjie Zi, MD

Role: PRINCIPAL_INVESTIGATOR

Neurology, Xinqiao Hospital of the Army Medical University

Locations

Xinqiao Hospital of Army Medical University

Chongqing, Chongqing Municipality, China

The Second Hospital of Jiaozuo

Jiaozuo, Henan, China

Wuhan No. 1 Hospital

Wuhan, Hubei, China

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

Hengyang, Hunan, China

Xiangtan Central Hospital

Xiangtan, Hunan, China

The 904th Hospital of CPLA

Wuxi, Jiangsu, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 32078683 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30128510 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29694815 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33464335 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40396577 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39435713 (View on PubMed)

Other Identifiers

BRIDGE-TNK

Identifier Type: -

Identifier Source: org_study_id