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Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events(TRACE)

Phase 2
Completed
Conditions
Acute Ischemic Stroke
Interventions
Registration Number
NCT04676659
Lead Sponsor
Beijing Tiantan Hospital
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
240
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 100Γ—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 .

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1 (rhTNK-tPA 0.10 mg/kg)TNK-tPADissolve one vial of rhTNK-tPA in 3 ml sterile water for injection to prepare a solution of 5.33 mg/ml. Calculate the required volume according to the body weight of the subject, then measure the required volume. Administer as a single 0.10 mg/kg IV bolus over 5-10 seconds.
Group 2 (rhTNK-tPA 0.25 mg/kg)TNK-tPADissolve one vial of rhTNK-tPA in 3 ml sterile water for injection to prepare a solution of 5.33 mg/ml. Calculate the required volume according to the body weight of the subject, then measure the required volume. Administer as a single 0.25 mg/kg IV bolus over 5-10 seconds.
Group 3 (rhTNK-tPA 0.32 mg/kg)TNK-tPADissolve one vial of rhTNK-tPA in 3 ml sterile water for injection to prepare a solution of 5.33 mg/ml. Calculate the required volume according to the body weight of the subject, then measure the required volume. Administer as a single 0.32 mg/kg IV bolus over 5-10 seconds.
Group 4 (rt-PA 0.9 mg/kg)TNK-tPA10% of rt-PA 0.9 mg/kg administered as an initial IV bolus followed by the remaining 90% as an IV infusion over the next 1 hour.
Primary Outcome Measures
NameTimeMethod
National Institutes of Health Stroke Scale (NIHSS)14 days

Proportion of subjects with NIHSS 1 or at least 4 on the NIHSS score decreased from the baseline at day14.

Secondary Outcome Measures
NameTimeMethod
National Institutes of Health Stroke Scale (NIHSS)90 days

Neurological impairment defined as change of NIHSS score at 90 days.

Barthel(BI)90 days

Global function of daily living defined as BI β‰₯ 95 at 90 days.

EQ-5D90 days

Quality of life measured by EQ-5D scale.

Modified Rankin Scale (mRS)90 days

1. Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 days.

2. Ordinal distribution of mRS and change of proportion of subjects with mRS (0-2) at 90 days.

Trial Locations

Locations (24)

ZhongShan Hospital ,FuDan University

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Shanghai, Shanghai, China

1st Hospital Affiliated to Zhengzhou University

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Zhengzhou, Henan, China

SiChuan University HuaXi Hospital

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Chengdu, Sichuan, China

Beijing Tiantan Hospital, Capital Medical University

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Beijing, Beijing, China

The Ninth People's Hospital of Chongqing

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Chongqing, Chongqing, China

HaiNan Provincial People's Hospital

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Haikou, Hainan, China

First Affiliated Hospital of Jinan University

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Guangzhou, Guangdong, China

Affiliated Hosptial to GuiZhou Medical University

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Guiyang, Guizhou, China

ShenZhen Hospital ,Beijing University

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Shenzhen, Guangdong, China

Tangshan Workers' Hospital

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Tangshan, Hebei, China

Hebei Medical University Third Hospital

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Shijiazhuang, Hebei, China

The First Hospital Of Qiqihar

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Qiqihar, Heilongjiang, China

Luoyang First People's Hosptical

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Luoyang, Henan, China

ChangSha 1st Municipal Hospital

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Changsha, Hunan, China

Inner Mongolia BaoGang Hospital

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Baotou, Inner Mongolia, China

Huai'an Second People's Hospital

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Huai'an, Jiangsu, China

Baotou Central Hospital

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Baotou, Inner Mongolia, China

First Hospital of Jilin University

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Chang chun, Jilin, China

Meihekou Central Hospital

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Tonghua, Jilin, China

First People 's Hospital Of Shenyang

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Shenyang, Liaoning, China

General Hospital of Northern War Zone , PLA

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Shenyang, Liaoning, China

Linyi People's Hospital

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Linyi, Shandong, China

HuaShan Hospital Affiliated to FuDan University

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Shanghai, Shanghai, China

Yantai Yuhuangding Hospital

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Yantai, Shandong, China

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