Clinical trial NCT04676659: Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events(TRACE)
Official title: Phase II Dose-finding Open Study of Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Injection Administered Within 3 Hours After Onset of Hyperacute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: rhTNK-tPA
acute
stroke
phaseII
Acute Ischemic Stroke
rt-PA
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
Collaborators: name: Guangzhou Recomgen Biotech Co., Ltd.
name: The First Hospital Of Qiqihar
name: Hebei Medical University Third Hospital
name: Yantai Yuhuangding Hospital
name: Fudan University
name: First Affiliated Hospital of Jinan University
name: The First Hospital of Jilin University
name: Huashan Hospital
name: West China Hospital
name: Inner Mongolia Baogang Hospital
name: Linyi People's Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Baotou Central Hospital
First posted: 2020-12-21
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, prospective, randomization, open label, active and parallel control
Primary purpose: TREATMENT

Brief summary: To explore the safe and efficacious dose of rhTNK-tPA injection administered within 3 hours after onset of hyperacute ischemic stroke; to provide dose evidence for phase III clinical trial.

Detailed description: To evaluate the safety and efficacy of rhTNK-tPA at different doses of 0.10 mg/kg, 0.25 mg/kg and 0.32 mg/kg compared with standard rt-PA intravenous thrombolytic therapy within 3 hours after onset of ischemic stroke. The primary objective of this study is to evaluate the differences of NIHSS scores among the four treatment groups at 14 days after intravenous thrombolysis.

Eligibility criteria: Inclusion Criteria:

1. Age over 18 years.
2. Time from onset to treatment \< 3 hours; the time symptoms start is defined as "the last moment they appear normal".
3. Diagnosis of ischemic stroke according to "2014 China Guideline for Diagnosis and Treatment of Acute Ischemic Stroke" with assessable neurological impairment e.g., language, motor function, cognitive impairment, gaze impairment, visual field deficit and/or visual neglect. Ischemic stroke is defined as sudden acute focal neurological impairment with suspected cerebral ischemia, hemorrhage ruled out by CT scan.
4. mRS \> 2 at the first onset or prior onset.
5. Baseline NIHSS score is \> 4 and \< 26.
6. Signed informed consent.

Exclusion Criteria:

1. Absolute contraindications:

   1.1 History of severe head trauma or stroke within 3 months; 1.2 Suspected subarachnoid hemorrhage; 1.3 Arterial puncture at a non-compressible site within the previous 1week; 1.4 History of intracranial hemorrhage; 1.5 Intracranial tumor, vascular malformation, or arterial aneurysm; 1.6 Recent intracranial or intraspinal surgery; 1.7 Systolic blood pressure ≧ 180 mm Hg, or diastolic blood pressure ≧ 100 mm Hg; Increased blood pressure; 1.8 Active internal bleeding ; 1.9 Acute bleeding tendency, including platelet count below 100×109/L or otherwise; 1.10 Heparin treatment was performed within 48 h ( APTT exceeded the upper limit of normal range ) ; 1.11 Warfarin has been taken orally , and the international standardized ratio is INR \> 1.7 or PT \> 15 s ; 1.12 Anticoagulant drugs such as thrombin inhibitor or Xa factor inhibitor , argatroban ( including new anticoagulants with unclear mechanism ) are currently being used , and various sensitive laboratory tests are abnormal ( such as live ) APTT , INR , Platelet count , Serpentine ECT of pulse enzyme setting time ; thrombin time TT or appropriate determination of Xa factor activity ) ; 1.13 Blood glucose \< 2.7 mmol/L; 1.14 CT showed multilobular infarction ( low density \> 1 / 3 cerebral hemisphere )
2. Relative contraindications : The risks and benefits of thrombolysis should be carefully considered and weighed in the following cases ( that is , although there is one or more relative contraindications , it is not absolutely impossible to thrombolysis ).

   2.1 Mild stroke or stroke with rapid improvement of symptoms; 2.2 Women in pregnancy ; 2.3 Symptoms of neurological impairment after seizures ; 2.4 There have been major surgical operations or serious injuries in the last 2 weeks; 2.5 There were gastrointestinal or urinary system bleeding in recent 3 weeks ; 2.6 History of myocardial infarction within 3 months.
3. Have been enrolled in rhTNK-tPA in pre-study or participated in other clinical trials within 3 months prior to screening.
4. Lactating women, or childbearing women who do not use effective contraception.
5. Known allergy to rhTNK-tPA and/or rt-PA or relevant excipients.
6. The researchers judged that not suitable to participate in this study or participate in this study may lead to greater risk for patients ;
7. Can not comply with the test program or follow-up requirements .

Primary outcomes:
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 14 days
Secondary outcomes:
measure: Modified Rankin Scale (mRS)
timeFrame: 90 days
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 90 days
measure: Barthel(BI)
timeFrame: 90 days
measure: EQ-5D
timeFrame: 90 days
Other outcomes:
measure: Symptomatic intracranial hemorrhage(sICH)
timeFrame: 36 hours
measure: Death
timeFrame: 90 days
measure: Asymptomatic intracranial hemorrhage
timeFrame: 90 days
measure: Hemorrhage in other parts
timeFrame: 90 days
measure: AE/SAE
timeFrame: 90 days
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The Ninth People's Hospital of Chongqing
state: Chongqing
city: Guangzhou
country: China
facility: First Affiliated Hospital of Jinan University
state: Guangdong
city: Shenzhen
country: China
facility: ShenZhen Hospital ,Beijing University
state: Guangdong
city: Guiyang
country: China
facility: Affiliated Hosptial to GuiZhou Medical University
state: Guizhou
city: Haikou
country: China
facility: HaiNan Provincial People's Hospital
state: Hainan
city: Shijiazhuang
country: China
facility: Hebei Medical University Third Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan Workers' Hospital
state: Hebei
city: Qiqihar
country: China
facility: The First Hospital Of Qiqihar
state: Heilongjiang
city: Luoyang
country: China
facility: Luoyang First People's Hosptical
state: Henan
city: Zhengzhou
country: China
facility: 1st Hospital Affiliated to Zhengzhou University
state: Henan
city: Changsha
country: China
facility: ChangSha 1st Municipal Hospital
state: Hunan
city: Baotou
country: China
facility: Baotou Central Hospital
state: Inner Mongolia
city: Baotou
country: China
facility: Inner Mongolia BaoGang Hospital
state: Inner Mongolia
city: Huai'an
country: China
facility: Huai'an Second People's Hospital
state: Jiangsu
city: Chang chun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Tonghua
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Shenyang
country: China
facility: First People 's Hospital Of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: General Hospital of Northern War Zone , PLA
state: Liaoning
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: HuaShan Hospital Affiliated to FuDan University
state: Shanghai
city: Shanghai
country: China
facility: ZhongShan Hospital ,FuDan University
state: Shanghai
city: Chengdu
country: China
facility: SiChuan University HuaXi Hospital
state: Sichuan
Study officials:
affiliation: IRB of Beijing Tiantan Hospital,Capital Medical University
name: Meng Wang, MD,ph.D
role: STUDY_DIRECTOR
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