Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅱ

Acute Ischemic Stroke Clinical Trial

— TRACE?  

Official title:

A Phase 3, Multicentre,Open-label, Randomised Controlled, Non-inferiority Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04797013
• Other study ID #: MK02-2020-01
• Status: Completed
• Phase: Phase 3
• Start date: June 12, 2021
• Est. completion date: July 15, 2022

Study information

• Verified date: January 2023
• Source: Beijing Tiantan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1430
• Est. completion date: July 15, 2022
• Est. primary completion date: May 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemia
• Ischemic Stroke

Intervention

Drug:
• rt-PA
Subjects will be randomized to rhTNK-tPA or rt-PA in a 1:1 ratio.
• rhTNK-tPA
Subjects will be randomized to rhTNK-tPA or rt-PA in a 1:1 ratio.

Locations

Country	Name	City	State
China	Inner Mongolia Baotou Hospita	Baotou	Inner Mongolia
China	Beijing luhe hospital capital medical university	Beijing	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	First Hospital of Jilin University	Changchun	Jilin
China	Heping hospital affiliated to changzhi medical college	Changzhi	Shanxi
China	Affiliated hospital of chengde medical university	Chengde	Hebei
China	Affiliated Hospital of Chifeng University	Chifeng	Inner Mongolia
China	Kashkten Mongolian Medicine Hospital	Chifeng	Inner Mongolia
China	Chongqing Three Gorges Central Hospital	Chongqing	Chongqing
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	General Hospital of Chinese Medicine and Coal	Datong	Shanxi
China	The fifth people's s hospital of datong	Datong	Shanxi
China	Guangdong Provincial Hospital of Traditional Chinese Medicine	Guangdong	Guangdong
China	Guizhou provincial people's hospital	Guiyang	Guizhou
China	The 2ad affiliated hospital of harbin medical university	Haerbin	Heilongjiang
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The first affiliated hospital of ustc	Hefei	Anhui
China	Inner Mongolia People'S Hospital	Hohhot	Inner Mongolia
China	Huai an second people's hospital	Huaian	Jiangsu
China	Second People's Hospital of Jiaozuo City	Jiaozuo	Henan
China	The Firet Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	The first hospital of lanzhou university	Lanzhou	Gansu
China	Linfen central hospital	Linfen	Shanxi
China	Linfen people's hospital	Linfen	Shanxi
China	Linyi City People Hospital	Linyi	Shandong
China	Lishui Central Hospital	Lishui	Zhejiang
China	Mianyang central hospital	Mianyang	Sichuan
China	Third Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Nanyang central hospital	Nanyang	Henan
China	Nanyang Nanshi Hospital	Nanyang	Henan
China	Nayang second general hospital	Nanyang	Henan
China	Pingmei Shenma Medical Group General Hospital	Pingdingshan	Henan
China	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	Yue bei people's hospital	Shaoguan	Guangdong
China	Central hospital affiliated to shenyang medical college	Shenyang	Liaoning
China	General Hospital of Northern War Zone, PLA	Shenyang	Liaoning
China	The first hospital of china medical university	Shenyang	Liaoning
China	The First People'S Hospital of Shenyang	Shenyang	Liaoning
China	The first hospital of hebei medical university	Shijiazhuang	Hebei
China	the Third Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Jilin neuropsychiaric hospital	Siping	Jilin
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Shanxi Cardiovascular Hospital	Taiyuan	Shanxi
China	Shanxi provincial prople's hospital	Taiyuan	Taiyuan
China	Jiangsu taizhou people's hopital	Taizhou	Jiangsu
China	Taizhou Enze Medical Center ( Group )	Taizhou	Zhejiang
China	Tangshan Workers ' Hospital	Tangshan	Hebei
China	Tengzhou Central People's Hospital	Tengzhou	Shandong
China	Meihekou Central Hospital	Tonghua	Jilin
China	Tonghua Central Hospital	Tonghua	Jilin
China	Wenzhou Central Hospital	Wenzhou	Zhejiang
China	The central hospital of wuhan	Wuhan	Hunan
China	Xianyang Hospital of Yan ' an University	Xianyang	Shanxi
China	Xinxiang first people's hospital	Xinxiang	Henan
China	Xinyang central hospital	Xinyang	Henan
China	The people's hospltal of xuancheng city	Xuancheng	Anhui
China	General Hospital of Xuzhou Mining Group	Xuzhou	Jiangsu
China	Xuzhou central hospital	Xuzhou	Jiangsu
China	Yantai Yuhuangding Hosopital	Yantai	Shandong
China	The first affiliated hospital of hebei north university	Zhangjiakou	Hebei
China	The first affiliated hospital of zhengzhou university	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	Guangzhou Recomgen Biotech Co., Ltd.

Country where clinical trial is conducted

China, 

References & Publications (26)

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Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy — View Citation

Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos 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. — View Citation

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. — View Citation

Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Symptomatic intracranial hemorrhage(sICH)	Proportion of subjects with symptomatic intracranial hemorrhage (sICH) at 36 hours.( defined by ECASSIII)	36 hours
Other	Asymptomatic intracranial hemorrhage	The incidence of asymptomatic intracranial hemorrhage at 90 days.	90 days
Other	PH2 intracranial hemorrhage	The incidence of PH2 intracranial hemorrhage within 90 days (according to SITS standards).	90 days
Other	Any intracranial hemorrhage	The incidence of any intracranial hemorrhage within 90 days.	90 days
Other	Systematic bleeding	The incidence of Systematic bleeding at 90 days.( defined by GUSTO)	90 days
Other	Deaths	Rate of Overall mortality at 90 days.	90 days
Other	AEs/SAEs	The incidence of adverse events(AEs) / severe adverse events(SAEs) at 90 days.	90 days
Primary	Excellent functional outcome	Proportion of subjects with mRS(0-1) at 90 days.	90 days
Secondary	Good functional outcome	Proportion of subjects with mRS(0-2) at 90 days.	90 days
Secondary	National Institutes of Health Stroke Scale (NIHSS)	Proportion of subjects with NIHSS score = 4 improved compared with baseline at 24 or with NIHSS 0-1 at 24 hours and 7 days.	24 hours,day7
Secondary	EQ-5D	Quality of life measured by EQ-5D scale.	90 days
Secondary	Barthel (BI)	Global function of daily living defined as BI = 95 at 90 days.	90 days
Secondary	Modified Rankin Scale(mRS)	Ordinal distribution of mRS at 90 days.	90 days