TRACEⅡ: Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅱ
Study Details
Study Description
Brief Summary
A Phase Ⅲ, Multicenter, Prospective, Randomized, Open Label, Blinded-endpoint (PROBE) Controlled Trial of Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) for Injection Versus Alteplase for Acute Ischemic Stroke Within 4.5 Hours
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Detailed Description
To test the hypothesis that rhTNK-tPA is non-inferior to alteplase in thrombolysis treatment when administered within 4.5 hours of ischemic stroke onset.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: rhTNK-tPA (0.25mg/kg) rhTNK-tPA (0.25mg/kg) is given as a single, intravenous bolus (within 5-10 seconds) immediately upon randomization. Maximum dose 25mg. |
Drug: rhTNK-tPA
Subjects will be randomized to rhTNK-tPA or rt-PA in a 1:1 ratio.
Other Names:
|
Active Comparator: rt-PA (0.9mg/kg) 10% dose of rt-PA (0.9 mg/kg) is given as bolus and the remainder in 1 hour. Maximum dose 90mg. |
Drug: rt-PA
Subjects will be randomized to rhTNK-tPA or rt-PA in a 1:1 ratio.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Modified Rankin Scale(mRS) [90 days]
Proportion of subjects with mRS(0-1) at 90 days.
Secondary Outcome Measures
- Modified Rankin Scale(mRS) [90 days]
Proportion of subjects with mRS(0-2) at 90 days.
- National Institutes of Health Stroke Scale (NIHSS) [24 hours,day7]
Proportion of subjects with NIHSS 0-1 at 24 hours and 7 days.
- EQ-5D [90 days]
Quality of life measured by EQ-5D scale.
- Barthel (BI) [90 days]
Global function of daily living defined as BI ≥ 95 at 90 days.
- Modified Rankin Scale(mRS) [90 days]
Ordinal distribution of mRS at 90 days.
- National Institutes of Health Stroke Scale (NIHSS) [24 hours,day7]
Proportion of subjects with NIHSS score ≥ 4 improved compared with baseline at 24 hours and 7 days.
Other Outcome Measures
- Symptomatic intracranial hemorrhage(sICH) [36 hours]
Proportion of subjects with symptomatic intracranial hemorrhage (sICH) at 36 hours.( defined by ECASSIII)
- Asymptomatic intracranial hemorrhage [90 days]
The incidence of asymptomatic intracranial hemorrhage at 90 days.
- PH2 intracranial hemorrhage [90 days]
The incidence of PH2 intracranial hemorrhage within 90 days (according to SITS standards).
- Any intracranial hemorrhage [90 days]
The incidence of any intracranial hemorrhage within 90 days.
- Systematic bleeding [90 days]
The incidence of Systematic bleeding at 90 days.( defined by GUSTO)
- Deaths [90 days]
Rate of Overall mortality at 90 days.
- AEs/SAEs [90 days]
The incidence of adverse events(AEs) / severe adverse events(SAEs) at 90 days.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥18 years old, no gender limitation;
-
The time from onset to treatment was < 4.5h;The time at which symptoms begin is defined as "the time at which they finally appear normal";
-
The clinical diagnosis was ischemic stroke (the diagnosis followed the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2018);
-
MRS before onset was 0-1 points
-
Baseline NIHSS 5-25(both included);
-
Informed consent from the patient or surrogate.
Exclusion Criteria:
-
Intended to proceed endovascular treatment;
-
NIHSS consciousness score >2;
-
Allergy to tenecteplase or alteplase;
-
Past history of intracranial hemorrhage ;
-
A history of severe head trauma or stroke within 3 months;
-
A history of intracranial or spinal surgery within 3 months;
-
A history of gastrointestinal or urinary bleeding within 3 weeks;
-
2 weeks of major surgery;
-
Arterial puncture was performed at the hemostasis site that was not easily compressed within 1 week;
-
Intracranial tumors (except neuroectodermal tumors, such as meningiomas), large intracranial aneurysms;
-
Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/extradural hematoma, etc.);
-
Active visceral bleeding;
-
Aortic arch dissection was found;
-
After active antihypertensive treatment, hypertension is still not under control: systolic blood pressure ≥180 mm Hg, or diastolic blood pressure ≥100 mm Hg;
-
Propensity for acute bleeding, including platelet counts of less than 100×109/ L or otherwise;
-
Blood glucose <2.8 mmol/L or >22.22 mmol/L;
-
Oral warfarin anticoagulant with INR>1.7 or PT>15 s;
-
Heparin treatment was received within 24 h;
-
Thrombin inhibitors or factor Xa inhibitors were used within 48 h;
-
Head CT or MRI showed a large infarction (infarcted area > 1/3 of the middle cerebral artery);
-
Subjects who are unable or unwilling to cooperate due to hemiplegia (Todd's palsy) after epileptic seizure or other neurological/psychiatric disorders;
-
Pregnant women, lactating women, or subjects who do not agree to use effective contraception during the trial;
-
Participation in other clinical trials within 3 months prior to screening;
-
Unsuitability or participation in this study as judged by the Investigator may result in subjects being exposed to greater risk.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | The first affiliated hospital of ustc | Hefei | Anhui | China | 230000 |
2 | The people's hospltal of xuancheng city | Xuancheng | Anhui | China | 242000 |
3 | Beijing luhe hospital capital medical university | Beijing | Beijing | China | 100000 |
4 | Beijing Tiantan Hospital, Capital Medical University | Beijing | Beijing | China | 100000 |
5 | Chongqing Three Gorges Central Hospital | Chongqing | Chongqing | China | 404100 |
6 | The first hospital of lanzhou university | Lanzhou | Gansu | China | 730000 |
7 | Guangdong Provincial Hospital of Traditional Chinese Medicine | Guangdong | Guangdong | China | 510000 |
8 | Yue bei people's hospital | Shaoguan | Guangdong | China | 512000 |
9 | Guizhou provincial people's hospital | Guiyang | Guizhou | China | 550000 |
10 | Affiliated hospital of chengde medical university | Chengde | Hebei | China | 067000 |
11 | The first hospital of hebei medical university | Shijiazhuang | Hebei | China | 050000 |
12 | the Third Hospital of Hebei Medical University | Shijiazhuang | Hebei | China | 050000 |
13 | Tangshan Workers ' Hospital | Tangshan | Hebei | China | 063000 |
14 | The first affiliated hospital of hebei north university | Zhangjiakou | Hebei | China | 075000 |
15 | Daqing Oilfield General Hospital | Daqing | Heilongjiang | China | 163000 |
16 | The 2ad affiliated hospital of harbin medical university | Haerbin | Heilongjiang | China | 150000 |
17 | Second People's Hospital of Jiaozuo City | Jiaozuo | Henan | China | 454150 |
18 | Nanyang central hospital | Nanyang | Henan | China | 473000 |
19 | Nanyang Nanshi Hospital | Nanyang | Henan | China | 473000 |
20 | Nayang second general hospital | Nanyang | Henan | China | 473000 |
21 | Pingmei Shenma Medical Group General Hospital | Pingdingshan | Henan | China | 467000 |
22 | Xinxiang first people's hospital | Xinxiang | Henan | China | 453000 |
23 | Xinyang central hospital | Xinyang | Henan | China | 464000 |
24 | The first affiliated hospital of zhengzhou university | Zhengzhou | Henan | China | 450000 |
25 | The central hospital of wuhan | Wuhan | Hunan | China | 430000 |
26 | Inner Mongolia Baotou Hospita | Baotou | Inner Mongolia | China | 014 |
27 | Affiliated Hospital of Chifeng University | Chifeng | Inner Mongolia | China | 024000 |
28 | Kashkten Mongolian Medicine Hospital | Chifeng | Inner Mongolia | China | 024000 |
29 | Inner Mongolia People'S Hospital | Hohhot | Inner Mongolia | China | 010000 |
30 | Huai an second people's hospital | Huaian | Jiangsu | China | 223001 |
31 | Jiangsu taizhou people's hopital | Taizhou | Jiangsu | China | 225300 |
32 | General Hospital of Xuzhou Mining Group | Xuzhou | Jiangsu | China | 221000 |
33 | Xuzhou central hospital | Xuzhou | Jiangsu | China | 221000 |
34 | Third Affiliated Hospital of Nanchang University | Nanchang | Jiangxi | China | 330000 |
35 | First Hospital of Jilin University | Changchun | Jilin | China | 130 |
36 | Jilin neuropsychiaric hospital | Siping | Jilin | China | 136000 |
37 | Tonghua Central Hospital | Tonghua | Jilin | China | 134000 |
38 | Meihekou Central Hospital | Tonghua | Jilin | China | 135000 |
39 | The Firet Affiliated Hospital of Jinzhou Medical University | Jinzhou | Liaoning | China | 121000 |
40 | Central hospital affiliated to shenyang medical college | Shenyang | Liaoning | China | 110000 |
41 | General Hospital of Northern War Zone, PLA | Shenyang | Liaoning | China | 110000 |
42 | The first hospital of china medical university | Shenyang | Liaoning | China | 110000 |
43 | The First People'S Hospital of Shenyang | Shenyang | Liaoning | China | 110000 |
44 | Linyi City People Hospital | Linyi | Shandong | China | 276000 |
45 | Tengzhou Central People's Hospital | Tengzhou | Shandong | China | 277559 |
46 | Yantai Yuhuangding Hosopital | Yantai | Shandong | China | 264000 |
47 | Huashan Hospital Affiliated to Fudan University | Shanghai | Shanghai | China | 200000 |
48 | Heping hospital affiliated to changzhi medical college | Changzhi | Shanxi | China | 046000 |
49 | General Hospital of Chinese Medicine and Coal | Datong | Shanxi | China | 037000 |
50 | The fifth people's s hospital of datong | Datong | Shanxi | China | 037000 |
51 | Linfen central hospital | Linfen | Shanxi | China | 041000 |
52 | Linfen people's hospital | Linfen | Shanxi | China | 041000 |
53 | First Hospital of Shanxi Medical University | Taiyuan | Shanxi | China | 030000 |
54 | Shanxi Cardiovascular Hospital | Taiyuan | Shanxi | China | 030000 |
55 | Xianyang Hospital of Yan ' an University | Xianyang | Shanxi | China | 712000 |
56 | Mianyang central hospital | Mianyang | Sichuan | China | 621000 |
57 | Shanxi provincial prople's hospital | Taiyuan | Taiyuan | China | 030000 |
58 | The Second Affiliated Hospital Zhejiang University School of Medicine | Hangzhou | Zhejiang | China | 310000 |
59 | Lishui Central Hospital | Lishui | Zhejiang | China | 323000 |
60 | Taizhou Enze Medical Center ( Group ) | Taizhou | Zhejiang | China | 318000 |
61 | Wenzhou Central Hospital | Wenzhou | Zhejiang | China | 325000 |
Sponsors and Collaborators
- Beijing Tiantan Hospital
- Guangzhou Recomgen Biotech Co., Ltd.
Investigators
- Study Director: Wei Sun, IRB of Beijing Tiantan Hospital,Capital Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
- Burgos AM, Saver JL. Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials. Stroke. 2019 Aug;50(8):2156-2162. doi: 10.1161/STROKEAHA.119.025080. Epub 2019 Jul 18.
- Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, Levi CR, Hsu C, Kleinig TJ, Fatar M, Leys D, Molina C, Wijeratne T, Curtze S, Dewey HM, Barber PA, Butcher KS, De Silva DA, Bladin CF, Yassi N, Pfaff JAR, Sharma G, Bivard A, Desmond PM, Schwab S, Schellinger PD, Yan B, Mitchell PJ, Serena J, Toni D, Thijs V, Hacke W, Davis SM, Donnan GA; EXTEND, ECASS-4, and EPITHET Investigators. Extending thrombolysis to 4·5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019 Jul 13;394(10193):139-147. doi: 10.1016/S0140-6736(19)31053-0. Epub 2019 May 22. Erratum in: Lancet. 2020 Jun 20;395(10241):1906.
- 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.
- Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5. Review.
- Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.
- Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, Ford I, Muir KW. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4):368-76. doi: 10.1016/S1474-4422(15)70017-7. Epub 2015 Feb 26.
- Kheiri B, Osman M, Abdalla A, Haykal T, Ahmed S, Hassan M, Bachuwa G, Al Qasmi M, Bhatt DL. Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. J Thromb Thrombolysis. 2018 Nov;46(4):440-450. doi: 10.1007/s11239-018-1721-3. Review.
- Kunz WG, Hunink MG, Almekhlafi MA, Menon BK, Saver JL, Dippel DWJ, Majoie CBLM, Jovin TG, Davalos A, Bracard S, Guillemin F, Campbell BCV, Mitchell PJ, White P, Muir KW, Brown S, Demchuk AM, Hill MD, Goyal M; HERMES Collaborators. Public health and cost consequences of time delays to thrombectomy for acute ischemic stroke. Neurology. 2020 Nov 3;95(18):e2465-e2475. doi: 10.1212/WNL.0000000000010867. Epub 2020 Sep 17.
- Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Rønning OM, Thommessen B, Amthor KF, Ihle-Hansen H, Kurz M, Tobro H, Kaur K, Stankiewicz M, Carlsson M, Morsund Å, Idicula T, Aamodt AH, Lund C, Næss H, Waje-Andreassen U, Thomassen L. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017 Oct;16(10):781-788. doi: 10.1016/S1474-4422(17)30253-3. Epub 2017 Aug 2.
- MK02-2020-01