BRIDGE-TNK: Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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 Design
Arms and Interventions
| 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:
Other: Endovascular treatment
endovascular treatment
Other Names:
|
| Active Comparator: Endovascular treatment alone group endovascular treatment alone |
Other: Endovascular treatment
endovascular treatment
Other Names:
|
Outcome Measures
Primary Outcome Measures
- modified Rankin scale score [90 days]
disability level
Secondary Outcome Measures
- 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) [90 days]
excellent outcome
- Proportion of patients functionally independent (mRS score 0 to 2) at 90 days [90 days]
functional independence
- Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3) [90 days]
ambulatory or bodily needs-capable or better
- Substantial reperfusion at initial angiogram [within 5 minutes at initial angiogram]
evaluate effect of tenecteplase on reperfusion
- Revascularization rates at 48 hours from randomization [at 48 hours from randomization]
evaluate vascular patency after treatment
- Early neurologic improvement [72 hours]
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
- Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L) [90 days]
Health-related quality of life
- Symptomatic/Asymptomatic intracranial hemorrhage within 48 hours [within 48 hours after endovascular treatment]
evaluate intracranial hemorrhage
- Mortality within 90 days [90 days]
evaluate death rate of the two treatment groups
- Parenchymal hematoma [within 48 hours after endovascular treatment]
evaluate intracranial hemorrhage
- Procedural-related complications and severe adverse events [within 90 days]
evaluate complications and any adverse events
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged 18 years or older;
-
Acute ischemic stroke confirmed by clinical symptoms or imaging examination;
-
MCA-M1 or -M2, basilar artery, or posterior cerebral artery-P1 occlusion proved by CTA/MRA;
-
Eligible for intravenous thrombolysis with TNK-tPA;
-
Time from stroke onset to randomization within 4.25 hours;
-
Written informed consent is obtained from patients and/or their legal representatives.
Exclusion Criteria:
-
CT or MR evidence of intracranial hemorrhage;
-
Contraindications of intravenous thrombolysis;
-
Currently in pregnant or lactating or serum beta HCG test is positive on admission;
-
Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys;
-
Current participation in another clinical trial
-
Arterial tortuosity and/or other arterial disease that would prevent the device from reaching the target vessel;
-
Patients with a preexisting neurological or psychiatric disease that would confound the neurological functional evaluations;
-
Patients with occlusions in multiple vascular territories (e.g. bilateral anterior circulation, or anterior/posterior circulation);
-
CT or MR evidence of mass effect or intracranial tumor (except small meningioma);
-
CT or MR angiography evidence of intracranial arteriovenous malformations or aneurysms;
-
Any terminal illness with life expectancy less than 6 months;
-
Unlikely to be available for 90-day follow-up.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Xinqiao Hospital of Army Medical University | Chongqing | Chongqing | China | 400037 |
| 2 | Maoming Traditional Chinese Medicine Hospital | Maoming | Guangdong | China | 525000 |
| 3 | Wuhan No. 1 Hospital | Wuhan | Hubei | China | 430000 |
| 4 | The 904th Hospital of CPLA | Wuxi | Jiangsu | China | 214000 |
| 5 | The First Affiliated Hospital of Jilin University | Changchun | Jilin | China | 130000 |
Sponsors and Collaborators
- Xinqiao Hospital of Chongqing
- CSPC RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD
Investigators
- Principal Investigator: 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- BRIDGE-TNK