Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-Ⅲ）

Acute Ischemic Stroke Clinical Trial

Official title:

Thrombolysis Treated by TNK-tPA in Acute Ischemic Stroke Patients: a Multi-center, Block Randomized, Positive Drug Parallel Control and Non-inferior Phase Ⅲ Trial, 3T Stroke-Ⅲ

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05745259
• Other study ID #: PR-FHSW-2022001F
• Status: Recruiting
• Phase: Phase 3
• Start date: October 26, 2022
• Est. completion date: March 29, 2024

Study information

• Verified date: February 2023
• Source: Beijing Tiantan Hospital
• Contact: Yongjun Wang
• Phone: 13911172565
• Email: yongjunwang111[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial is prospective, randomized, open-label, blinded endpoint (PROBE) design. Patients with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be randomized 1:1 to 0.25mg/kg or 0.9 mg/kg alteplase before all participants undergo endovascular thrombectomy.

Description:

The study will be a multi-center, prospective, randomized, open- label, blinded endpoint (PROBE), controlled phase 3 trial (2 arm with 1:1 randomization) in ischemic stroke patients. Imagine is performed with CT or MRI acutely with imaging follow-up at 24-36 hours. The sample size is 1630.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1630
• Est. completion date: March 29, 2024
• Est. primary completion date: November 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 18=Age=80 years old;
• The clinical diagnosis was Acute ischemic stroke 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";
• MRS before onset was =1 points;
• Baseline NIHSS (at the time of randomization) should be =5 and =25 points;
• Informed consent from the patient or surrogate.

Exclusion Criteria:

• Intracranial hemorrhage identified by CT or MRI (CMBs detected by SWI is not counted);
• Massive anterior cerebral infarction identified by CT or MRI (ASPECT < 6 or lesions larger than one third of the territory of the middle cerebral artery or with a volume larger than 70mL)
• Patients planning to receive endovascular therapy
• A history of severe CNS damage (such as aneurysm or arteriovenous malformation, craniocerebral trauma, intracranial or spinal cord surgery)
• Onset with seizures, and the paralysis was suspected to be related to Todd paralysis.
• Administration of heparin within 48 hours preceding the onset of stroke with a baseline APTT exceeding the upper limit of the normal range.
• Oral anticoagulant (such as warfarin) treatment with baseline INR>1.7 or PT>15 s;
• Administration of thrombin inhibitors or factor Xa inhibitors within 48 hours preceding the onset of stroke with abnormal coagulation parameters or platelet count;
• BP couldn't be controlled with aggressive treatment. Uncontrolled hypertension was defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, measured for three times every 10 minutes.
• Platelet count of less than 100×109/ L;
• Blood glucose <50 mg/dl (<2.8 mmol/L) or >400 mg/dl (22.22 mmol/L);
• History of intracranial hemorrhage or active hemorrhagic disease. (Such as gastrointestinal, urinary tract or retinal bleeding)
• Tumors with an increased risk of bleeding.
• Prolonged or traumatic cardiopulmonary resuscitation (>2 min), delivery within the last 10 days or recent puncture of non-compression vessels such as subclavian vein or jugular vein
• Acute pancreatitis or severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varicose veins, and active hepatitis;
• Aortic arch dissection;
• Major surgery or severe trauma in the past 2 weeks;
• Subjects had serious, fatal, or disabling disease with an expected survival of less than 3 months;
• Unable to complete neurological assessment and follow-up visits because of dementia or mental illness;
• Pregnant women, lactating women, or have positive pregnancy test;
• Allergy to tenecteplase or alteplase or their components;
• Participation in other clinical trials within 3 months prior to screening;
• Unsuitable to involve in this study or would result in increased risk, as judged by the investigators.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Alteplase
Alteplase 0.9mg/kg are being used.
• Tenecteplase
Tenecteplase 0.25mg/kg are being used.

Locations

Country	Name	City	State
China	Anyang People's Hospital	Anyang	Henan
China	Baogang Hospital of Inner Monglia	Baotou	Inner Monglia
China	Baotou Central Hospital	Baotou	Inner Mongolia
China	Beijing Tiantan Hospital, Capital Medical University Beijing	Beijing	Beijing
China	Xuanwu Hospital Capital Medical University	Beijing	Beijing
China	Beipiao Central Hospital	Beipiao	Liaoning
China	The First Hospital of Jilin University	Changchun	Jilin
China	Keshenketengqi Mongolian Medicine Hospital	Chifeng	Inner Mongolia
China	Three Gorges Hospital Affiliated to Chongqing University	Chongqing	Chongqing
China	Dalian Central Hospital	Dalian	Liaoning
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	Daqing People's Hospital	Daqing	Heilongjiang
China	Sinopharm Coal Mine General Hospital	Datong	Shanxi
China	Dazhu County People's Hospital	Dazhu	Sichuan
China	Dezhou Hospital of Shandong University Qilu Hospital (Dezhou People's Hospital)	Dezhou	Shandong
China	Fushun Mining Bureau General Hospital	Fushun	Liaoning
China	Liaoning Health Industry Group Fuxin Mine General Hospital	Fuxin	Liaoning
China	Handan Central Hospital	Handan	Hebei
China	Hengshui people's Hospital (Harrison International Peace Hospital)	Hengshui	Hebei
China	The Third People's Hospital of Huizhou	Huizhou	Guangdong
China	Jiaozuo People's Hospital	Jiaozuo	Henan
China	Jinan People's Hospital	Jinan	Shandong
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	The First People's Hospital of Jingzhou	Jingzhou,	Hubei
China	The First Affiliated Hospital of Jinzhou Medical University	Jinzhou	Liaoning
China	Lanzhou University First Hospital	Lanzhou	Gansu
China	Liaocheng People's Hospital	Liaocheng	Shandong
China	Linfen Central Hospital	Linfen	Shanxi
China	Linfen People's Hospital	Linfen	Shanxi
China	Linyi Hospital of Traditional Chinese Medicine	Linyi	Shandong
China	Linyi People's Hospital	Linyi	Shandong
China	The First People's Hospital of Tancheng County	Linyi	Shandong
China	Mianyang Central Hospital	Mianyang	Sichuan
China	Nanyang South Stone Hospital	Nanyang	Henan
China	Pingmei Shenma medical group general hospital	Pingdingshan	Henan
China	Quanzhou First Hospital	Quanzhou	Fujian
China	Yuebei People's Hospital	Shaoguan	Guangdong
China	Affiliated Central Hospital of Shenyang Medical College	ShenYang	Liaoning
China	Air Force Hospital of Northern War Zone,PLA	Shenyang	Liaoning
China	General Hospital of Northern War Zone,PLA	Shenyang	Liaoning
China	The First Affiliated Hospital of China Medical University	ShenYang	Liaoning
China	The First People's Hospital of Shenyang	Shenyang	Liaoning
China	Jilin Guowen Hospital	Siping	Jilin
China	Siping Central People's Hospital	Siping	Jilin
China	The Second Affiliated Hospital of Suzhou Medical University	Suzhou	Jiangsu
China	Taian Central Hospital (Tai 'an Central Hospital of Qingdao University, Tai 'an Medical and Nursing Center)	Taian	Shandong
China	Shanxi Cardiovascular Disease Hospital	Taiyuan	Shanxi
China	Taizhou People's Hospital	Taizhou	Jiangsu
China	Tangshan Workers' Hospital	Tangshan	Hebei
China	Tengzhou Central Hospital	Tengzhou	Shandong
China	Meihekou Central Hospital	Tonghua	Jilin
China	Tonghua Central Hospital	Tonghua	Jilin
China	Weifang Hospital of Traditional Chinese Medicine	Weifang	Shandong
China	Xinxiang Central Hospital	Xinxiang	Henan
China	Xuancheng People's Hospital	Xuancheng	Anhui
China	The Affiliated Hospital of Xuhzou Meidcal University	Xuzhou	Jiangsu
China	Xuzhou Central Hospital	Xuzhou	Jiangsu
China	Xuzhou Mining Group General Hospital	Xuzhou	Jiangsu
China	Yantai Yuhangding Hospital	Yantai	Shandong
China	General Hospital of Ningxia Medical University Cardio-cerebral Vascular Disease Hospital	Yinchuan	Ningxia
China	The First People's Hospital of Yinchuan	Yinchuan	Ningxia
China	The First People's Hospital of Yulin	Yulin	Guangxi
China	Zhoukou Downtown Hospital	Zhoukou	Henan

Sponsors (3)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	Jiangsu FENG HUA Biotech Pharmaceutical Co., Ltd, The Place Pharmaceutical(Jiangsu) Co., Ltd

Country where clinical trial is conducted

China, 

References & Publications (19)

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Standards and procedures for rapid reporting of safety data during drug clinical trials

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Symptomatic intracranial hemorrhage(sICH)	Incidence of symptomatic intracranial hemorrhage (sICH) within 24~36 hours.( According to ECASS ? and SITS-MOST)	24~36 hours post treatment
Other	Parenchymal hematoma intracranial hemorrhage (type PH2, SITS-MOST)	Incidence of intracranial hemorrhage (type PH2, SITS-MOST) within 24~36 hours.	24~36 hours post treatment
Other	Any intracranial hemorrhage	Incidence of any intracranial hemorrhage within 24~36 hours.	24~36 hours post treatment
Other	Systematic bleeding	Incidence of Systematic bleeding within 36 hours. (defined by GUSTO)	36 hours
Other	Deaths	Vascular mortality at 90±7 days (mainly due to stroke, myocardial infarction or pulmonary embolism)	90±7 days
Other	Deaths	Mortality due to any cause at 90±7days.	90±7 days
Other	SAEs	Incidence of severe adverse events(SAEs) at 90±7 days.	90±7 days
Other	AEs	Incidence of adverse events(AEs) at 90±7 days.	90±7 days
Primary	Modified Rankin Scale(mRS)	Proportion of subjects with mRS scores of (0-1) at 90±7 days.	90±7 days
Secondary	National Institutes of Health Stroke Scale (NIHSS)	NIHSS score at 24±2 hours.	24±2 hours
Secondary	National Institutes of Health Stroke Scale (NIHSS)	Proportion of subjects with = 4 point reduction in NIHSS or reaching 0-1 at 7 ± 2 days or before discharge (whichever occurs first)	7±2days or discharge
Secondary	Modified Rankin Scale(mRS)	Proportion of subjects with mRS scores of (0-2) at 90±7 days.	90±7 days
Secondary	Modified Rankin Scale(mRS)	mRS scores at 90±7 days.	90±7 days
Secondary	The new vascular events	Incidence of the new vascular events, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardio-cerebral revascularization at 90±7 days. (including: carotid endarterectomy, intracranial and extracranial artery interventional therapy, intracranial and extracranial artery bypass surgery, coronary interventional or bypass therapy)	90±7 days
Secondary	EQ-5D	EQ-5D scores at 90±7 days.	90±7 days