Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-II）
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Alteplase Patients will receive intravenous Alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour. |
Drug: Alteplase
Alteplase 0.9mg/kg are being used.
Other Names:
|
| Experimental: Tenecteplase 0.25mg/kg Patients will receive intravenous Tenecteplase, 0.25mg/kg, maximum 25mg, administered as a bolus over 5~10 seconds |
Drug: Tenecteplase
Tenecteplase 0.25mg/kg are being used.
Other Names:
|
| Experimental: Tenecteplase 0.4mg/kg Patients will receive intravenous Tenecteplase, 0.4mg/kg, maximum 40mg, administered as a bolus over 5~10 seconds |
Drug: Tenecteplase
Tenecteplase 0.4mg/kg are being used.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Modified Rankin Scale(mRS) [90±7 days]
Proportion of subjects with mRS scores of (0-1) at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)
Secondary Outcome Measures
- National Institutes of Health Stroke Scale (NIHSS) [24±2 hours]
NIHSS score at 24±2 hours.(Comments:The minimum and maximum values are from 0 to 40, and higher scores mean a worse outcome.)
- National Institutes of Health Stroke Scale (NIHSS) [7±2days or discharge]
Proportion of subjects with ≥ 4 point reduction in NIHSS or reaching 0-1 at 7 ± 2 days or before discharge (whichever occurs first).(Comments:The minimum and maximum values are from 0 to 40, and higher scores mean a worse outcome.)
- Modified Rankin Scale(mRS) [90±7 days]
Proportion of subjects with mRS scores of (0-2) at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)
- Modified Rankin Scale(mRS) [90±7 days]
mRS scores at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)
- The new vascular events [90±7 days]
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)
- Deaths [90±7 days]
Vascular mortality at 90±7 days (mainly due to stroke, myocardial infarction or pulmonary embolism)
- EQ-5D [90±7 days]
EQ-5D scores at 90±7 days.(Comments:The minimum and maximum values are from 0 to 100,and higher scores mean a better outcome.)
Other Outcome Measures
- Symptomatic intracranial hemorrhage(sICH) [24~30 hours post treatment]
Incidence of symptomatic intracranial hemorrhage (sICH) within 24~30 hours.( According to ECASSII)
- Parenchymal hematoma type 2(PH2) intracranial hemorrhage [24~30 hours post treatment]
Incidence of intracranial hemorrhage (PH2) within 24~30 hours.
- Any intracranial hemorrhage [24~30 hours post treatment]
Incidence of any intracranial hemorrhage within 24~30 hours.
- Systematic bleeding [30 hours]
Incidence of Systematic bleeding within 30 hours. ( defined by PLATO)
- Deaths [90±7 days]
Mortality due to any cause at 90±7days.
- AEs/SAEs [90±7 days]
Incidence of adverse events(AEs) / severe adverse events(SAEs) at 90±7 days.
Eligibility Criteria
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;
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Baseline NIHSS (at the time of randomization) should be > 5 and ≤25 points;
-
Informed consent from the patient or surrogate.
Exclusion Criteria:
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Intracranial hemorrhage identified by CT or MRI (CMBs detected by SWI is not counted);
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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)
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A history of severe CNS damage (such as aneurysm or arteriovenous malformation, craniocerebral trauma, intracranial or spinal cord surgery)
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Onset with seizures, and the paralysis was suspected to be related to Todd paralysis.
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Administration of heparin within 48 hours preceding the onset of stroke with a baseline APTT exceeding the upper limit of the normal range.
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Oral anticoagulant (such as warfarin) treatment with baseline INR>1.7 or PT>15 s;
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Administration of thrombin inhibitors or factor Xa inhibitors within 48 hours preceding the onset of stroke with abnormal coagulation parameters or platelet count;
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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.
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Platelet count of less than 100×109/ L;
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Blood glucose <50 mg/dl (<2.8 mmol/L) or >400 mg/dl (22.22 mmol/L);
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History of intracranial hemorrhage or active hemorrhagic disease. (Such as gastrointestinal, urinary tract or retinal bleeding)
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Tumors with an increased risk of bleeding.
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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
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Acute pancreatitis or severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varicose veins, and active hepatitis;
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Aortic arch dissection;
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Major surgery or severe trauma in the past 2 weeks;
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Subjects had serious, fatal, or disabling disease with an expected survival of less than 3 months;
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Unable to complete neurological assessment and follow-up visits because of dementia or mental illness;
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Pregnant women, lactating women, or have positive pregnancy test;
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Allergy to tenecteplase or alteplase or their components;
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Participation in other clinical trials within 3 months prior to screening;
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Unsuitable to involve in this study or would result in increased risk, as judged by the investigators.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tiantan Hospital, Capital Medical University Beijing | Beijing | Beijing | China | 100000 |
| 2 | Quanzhou First Hospital | Quanzhou | Fujian | China | 362000 |
| 3 | Yue Bei People'S Hospital | Shaoguan | Guangdong | China | 512000 |
| 4 | Hengshui people's Hospital (Harrison International Peace Hospital) | Hengshui | Hebei | China | 053000 |
| 5 | Tangshan Gongren Hospital | Tangshan | Hebei | China | 063000 |
| 6 | Daqing Oilfield General Hospital | Daqing | Heilongjiang | China | 163000 |
| 7 | Baogang Hospital of Inner Monglia | Baotou | Inner Monglia | China | 014010 |
| 8 | Inner Mongolia Baotou Hospital | Baotou | Inner Mongolia | China | 014040 |
| 9 | Huai'an Second People's Hospital | Huai'an | Jiangsu | China | 121000 |
| 10 | The Affiliated Hospital of Xuzhou Meidcal University | Xuzhou | Jiangsu | China | 221006 |
| 11 | The First Hospital of Jilin University | Changchun | Jilin | China | 130021 |
| 12 | Mei He Kou Central Hospital | Meihekou | Jilin | China | 135000 |
| 13 | Jilin Guowen Hospital | Siping | Jilin | China | 136100 |
| 14 | The First People's Hospital of Yinchuan | Yinchuan | Ningxia | China | 750001 |
| 15 | General Hospital of Ningxia Medical University | Yinchuan | Ningxia | China | 750004 |
| 16 | Shandong Provincial Third Hospital | Jinan | Shandong | China | 250000 |
| 17 | Liaocheng People'S Hospital | Liaocheng | Shandong | China | 252006 |
| 18 | Linyi City People Hospital | Linyi | Shandong | China | 276000 |
| 19 | Qingdao Central Hospital | Qingdao | Shandong | China | 266000 |
| 20 | Yantai Yuhangding Hospital | Yantai | Shandong | China | 264000 |
| 21 | Shanghai Pudong Hospital | Shanghai | Shanghai | China | 201200 |
| 22 | Changzhi People'S Hospital | Changzhi | Shanxi | China | 046000 |
| 23 | The First People's Hospital of Jinzhong | Jinzhong | Shanxi | China | 030602 |
| 24 | First Hospital of Shanxi Medical University | Taiyuan | Shanxi | China | 030001 |
| 25 | Dazhu County People's Hospital | Dazhou | Sichuan | China | 635199 |
| 26 | Zigong First People'S Hospital | Zigong | Sichuan | China | 643000 |
| 27 | Zhejiang Provincial People'S Hospital | Hangzhou | Zhejiang | China | 310000 |
| 28 | Taizhou Hospital of Zhejiang Province | Taizhou | Zhejiang | China | 318000 |
Sponsors and Collaborators
- Beijing Tiantan Hospital
- Jiangsu FENG HUA Biotech Pharmaceutical Co., Ltd
- The Place Pharmaceutical(Jiangsu) Co., Ltd
Investigators
- Study Director: Shuya Li, IRB of Beijing Tiantan Hospital,Capital Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PR-SMTJ-2019001F