Clinical trial NCT05745259: Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-Ⅲ）
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: TNK-tPA, rt-PA, Acute stroke, phase Ⅲ trial
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu FENG HUA Biotech Pharmaceutical Co., Ltd
name: The Place Pharmaceutical(Jiangsu) Co., Ltd
First posted: 2023-02-27
Enrollment: 1630
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Modified Rankin Scale(mRS)
timeFrame: 90±7 days
Secondary outcomes:
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 24±2 hours
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 7±2days or discharge
measure: Modified Rankin Scale(mRS)
timeFrame: 90±7 days
measure: Modified Rankin Scale(mRS)
timeFrame: 90±7 days
measure: The new vascular events
timeFrame: 90±7 days
measure: EQ-5D
timeFrame: 90±7 days
Other outcomes:
measure: Symptomatic intracranial hemorrhage(sICH)
timeFrame: 24~36 hours post treatment
measure: Parenchymal hematoma intracranial hemorrhage (type PH2, SITS-MOST)
timeFrame: 24~36 hours post treatment
measure: Any intracranial hemorrhage
timeFrame: 24~36 hours post treatment
measure: Systematic bleeding
timeFrame: 36 hours
measure: Deaths
timeFrame: 90±7 days
measure: Deaths
timeFrame: 90±7 days
measure: SAEs
timeFrame: 90±7 days
measure: AEs
timeFrame: 90±7 days
Locations:
city: Xuancheng
country: China
facility: Xuancheng People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University Beijing
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: Three Gorges Hospital Affiliated to Chongqing University
state: Chongqing
city: Quanzhou
country: China
facility: Quanzhou First Hospital
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University First Hospital
state: Gansu
city: Huizhou
country: China
facility: The Third People's Hospital of Huizhou
state: Guangdong
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Yulin
country: China
facility: The First People's Hospital of Yulin
state: Guangxi
city: Handan
country: China
facility: Handan Central Hospital
state: Hebei
city: Hengshui
country: China
facility: Hengshui people's Hospital (Harrison International Peace Hospital)
state: Hebei
city: Tangshan
country: China
facility: Tangshan Workers' Hospital
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Daqing
country: China
facility: Daqing People's Hospital
state: Heilongjiang
city: Anyang
country: China
facility: Anyang People's Hospital
state: Henan
city: Jiaozuo
country: China
facility: Jiaozuo People's Hospital
state: Henan
city: Nanyang
country: China
facility: Nanyang South Stone Hospital
state: Henan
city: Pingdingshan
country: China
facility: Pingmei Shenma medical group general hospital
state: Henan
city: Xinxiang
country: China
facility: Xinxiang Central Hospital
state: Henan
city: Zhoukou
country: China
facility: Zhoukou Downtown Hospital
state: Henan
city: Jingzhou,
country: China
facility: The First People's Hospital of Jingzhou
state: Hubei
city: Baotou
country: China
facility: Baogang Hospital of Inner Monglia
state: Inner Monglia
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia
city: Chifeng
country: China
facility: Keshenketengqi Mongolian Medicine Hospital
state: Inner Mongolia
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Suzhou Medical University
state: Jiangsu
city: Taizhou
country: China
facility: Taizhou People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Mining Group General Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuhzou Meidcal University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Siping
country: China
facility: Jilin Guowen Hospital
state: Jilin
city: Siping
country: China
facility: Siping Central People's Hospital
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Tonghua
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Beipiao
country: China
facility: Beipiao Central Hospital
state: Liaoning
city: Dalian
country: China
facility: Dalian Central Hospital
state: Liaoning
city: Fushun
country: China
facility: Fushun Mining Bureau General Hospital
state: Liaoning
city: Fuxin
country: China
facility: Liaoning Health Industry Group Fuxin Mine General Hospital
state: Liaoning
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: ShenYang
country: China
facility: Affiliated Central Hospital of Shenyang Medical College
state: Liaoning
city: Shenyang
country: China
facility: Air Force Hospital of Northern War Zone,PLA
state: Liaoning
city: Shenyang
country: China
facility: General Hospital of Northern War Zone,PLA
state: Liaoning
city: ShenYang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First People's Hospital of Shenyang
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University Cardio-cerebral Vascular Disease Hospital
state: Ningxia
city: Yinchuan
country: China
facility: The First People's Hospital of Yinchuan
state: Ningxia
city: Dezhou
country: China
facility: Dezhou Hospital of Shandong University Qilu Hospital (Dezhou People's Hospital)
state: Shandong
city: Jinan
country: China
facility: Jinan People's Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Hospital of Traditional Chinese Medicine
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Linyi
country: China
facility: The First People's Hospital of Tancheng County
state: Shandong
city: Taian
country: China
facility: Taian Central Hospital (Tai 'an Central Hospital of Qingdao University, Tai 'an Medical and Nursing Center)
state: Shandong
city: Tengzhou
country: China
facility: Tengzhou Central Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang Hospital of Traditional Chinese Medicine
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhangding Hospital
state: Shandong
city: Datong
country: China
facility: Sinopharm Coal Mine General Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen People's Hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Disease Hospital
state: Shanxi
city: Dazhu
country: China
facility: Dazhu County People's Hospital
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
Study officials:
affiliation: IRB of Beijing Tiantan Hospital,Capital Medical University
name: Shuya Li
role: STUDY_DIRECTOR
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