Clinical trial NCT04733742: Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Stroke, Acute
Stroke, Ischemic
Keywords: Thrombolysis
Endovascular treatment
rhTNK-tPA
Lead sponsor: Xinqiao Hospital of Chongqing
Sponsor class: OTHER
Collaborators: name: CSPC RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD
First posted: 2021-02-02
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Proportion of patients functionally independent (mRS score 0 to 2) at 90 days
timeFrame: 90 days
Secondary outcomes:
measure: Substantial reperfusion at initial angiogram
timeFrame: within 5 minutes at initial angiogram
measure: Successful reperfusion at end-of-procedure angiography
timeFrame: 15 minutes after initial angiogram
measure: First-pass reperfusion
timeFrame: After artery puncture, but before thrombectomy
measure: Modified first-pass reperfusion
timeFrame: After artery puncture, but before thrombectomy
measure: National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: 5 to 7 days or discharge
measure: modified Rankin scale score
timeFrame: 90 days
measure: 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)
timeFrame: 90 days
measure: Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3)
timeFrame: 90 days
measure: Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L)
timeFrame: 90 days
measure: Any radiologic intracranial hemorrhage within 48 hours
timeFrame: within 48 hours after endovascular treatment
measure: Symptomatic intracranial hemorrhage within 48 hours
timeFrame: within 48 hours after endovascular treatment
measure: Mortality within 90 days
timeFrame: 90 days
measure: Procedural-related complications
timeFrame: within 90 days
measure: Severe adverse events
timeFrame: within 90 days
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Xinqiao Hospital of Army Medical University
state: Chongqing
city: Jiaozuo
country: China
facility: The Second Hospital of Jiaozuo
state: Henan
city: Wuhan
country: China
facility: Wuhan No. 1 Hospital
state: Hubei
city: Hengyang
country: China
facility: The First Affiliated Hospital, Hengyang Medical School, University of South China
state: Hunan
city: Xiangtan
country: China
facility: Xiangtan Central Hospital
state: Hunan
city: Wuxi
country: China
facility: The 904th Hospital of CPLA
state: Jiangsu
Study officials:
affiliation: Neurology, Xinqiao Hospital of the Army Medical University
name: Qingwu Yang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Marcus Stroke & Neuroscience Center, Grady Memorial Hospital, Emory University, Atlanta, USA
name: Raul G Nogueira, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology, University of California, Los Angeles, USA
name: Jeffrey L Saver, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Neurology, Xinqiao Hospital of the Army Medical University
name: Wenjie Zi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
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, 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.