Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke

Stroke, Acute Clinical Trial

— BRIDGE-TNK  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04733742
• Other study ID #: BRIDGE-TNK
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 9, 2022
• Est. completion date: March 30, 2026

Study information

• Verified date: May 2024
• Source: Xinqiao Hospital of Chongqing
• Contact: Zhongming Qiu, MD
• Phone: +8613236599269
• Email: qiuzhongmingdoctor[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 544
• Est. completion date: March 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Aged 18 years or older;

2. Acute ischemic stroke confirmed by clinical symptoms or imaging examination;

3. Internal carotid artery (cervical or intracranial), 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.

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke
• Stroke, Acute
• Stroke, Ischemic

Intervention

Drug:
• rhTNK-tPA
intravenous thrombolysis with rhTNK-tPA followed by endovascular treatment

Other:
• Endovascular treatment
endovascular treatment

Locations

Country	Name	City	State
China	Xinqiao Hospital of Army Medical University	Chongqing	Chongqing
China	The First Affiliated Hospital, Hengyang Medical School, University of South China	Hengyang	Hunan
China	The Second Hospital of Jiaozuo	Jiaozuo	Henan
China	Wuhan No. 1 Hospital	Wuhan	Hubei
China	The 904th Hospital of CPLA	Wuxi	Jiangsu
China	Xiangtan Central Hospital	Xiangtan	Hunan

Sponsors (2)

Lead Sponsor	Collaborator
Xinqiao Hospital of Chongqing	CSPC RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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, Ch — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients functionally independent (mRS score 0 to 2) at 90 days	functional independence	90 days
Secondary	Substantial reperfusion at initial angiogram	evaluate effect of tenecteplase on reperfusion	within 5 minutes at initial angiogram
Secondary	Successful reperfusion at end-of-procedure angiography	evaluate vascular patency after thrombectomy	15 minutes after initial angiogram
Secondary	National Institutes of Health Stroke Scale (NIHSS) score	Neurological status	5 to 7 days or discharge
Secondary	modified Rankin scale score	disability level	90 days
Secondary	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
Secondary	Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3)	ambulatory or bodily needs-capable or better	90 days
Secondary	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
Secondary	Symptomatic/Asymptomatic intracranial hemorrhage within 48 hours	evaluate intracranial hemorrhage	within 48 hours after endovascular treatment
Secondary	Mortality within 90 days	evaluate death rate of the two treatment groups	90 days
Secondary	Parenchymal hematoma	evaluate intracranial hemorrhage	within 48 hours after endovascular treatment
Secondary	Procedural-related complications and severe adverse events	evaluate complications and any adverse events	within 90 days