Clinical trial NCT05281549: Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-II）
Official title: Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients: a Multi-center, Block Randomized, Positive Drug Parallel Controlled Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: TNK-tPA
rt-PA
Acute stroke
phase II 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: 2022-03-16
Enrollment: 225
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 trial is prospective, block 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 1:1:1 to 0.25mg/kg or 0.40mg/kg intravenous tenecteplase 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 2 trial (3 arm with 1:1:1 randomization) in ischemic stroke patients. Imagine is performed with CT or MRI acutely with imaging follow-up at 24-30 hours. The sample size is 225.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 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)
* 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: Deaths
timeFrame: 90±7 days
measure: EQ-5D
timeFrame: 90±7 days
Other outcomes:
measure: Symptomatic intracranial hemorrhage(sICH)
timeFrame: 24~30 hours post treatment
measure: Parenchymal hematoma type 2(PH2) intracranial hemorrhage
timeFrame: 24~30 hours post treatment
measure: Any intracranial hemorrhage
timeFrame: 24~30 hours post treatment
measure: Systematic bleeding
timeFrame: 30 hours
measure: Deaths
timeFrame: 90±7 days
measure: AEs/SAEs
timeFrame: 90±7 days
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University Beijing
state: Beijing
city: Quanzhou
country: China
facility: Quanzhou First Hospital
state: Fujian
city: Shaoguan
country: China
facility: Yue Bei People'S Hospital
state: Guangdong
city: Hengshui
country: China
facility: Hengshui people's Hospital (Harrison International Peace Hospital)
state: Hebei
city: Tangshan
country: China
facility: Tangshan Gongren Hospital
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Baotou
country: China
facility: Baogang Hospital of Inner Monglia
state: Inner Monglia
city: Baotou
country: China
facility: Inner Mongolia Baotou Hospital
state: Inner Mongolia
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Meidcal University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Meihekou
country: China
facility: Mei He Kou Central Hospital
state: Jilin
city: Siping
country: China
facility: Jilin Guowen Hospital
state: Jilin
city: Yinchuan
country: China
facility: The First People's Hospital of Yinchuan
state: Ningxia
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Shandong Provincial Third Hospital
state: Shandong
city: Liaocheng
country: China
facility: Liaocheng People'S Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi City People Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Central Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Pudong Hospital
state: Shanghai
city: Changzhi
country: China
facility: Changzhi People'S Hospital
state: Shanxi
city: Jinzhong
country: China
facility: The First People's Hospital of Jinzhong
state: Shanxi
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Dazhou
country: China
facility: Dazhu County People's Hospital
state: Sichuan
city: Zigong
country: China
facility: Zigong First People'S Hospital
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial People'S Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: IRB of Beijing Tiantan Hospital,Capital Medical University
name: Shuya Li
role: STUDY_DIRECTOR
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