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Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events(TRACE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04676659
Recruitment Status : Completed
First Posted : December 21, 2020
Last Update Posted : December 21, 2020
Sponsor:
Collaborators:
Guangzhou Recomgen Biotech Co., Ltd.
The First Hospital Of Qiqihar
Hebei Medical University Third Hospital
Yantai Yuhuangding Hospital
Fudan University
First Affiliated Hospital of Jinan University
The First Hospital of Jilin University
Huashan Hospital
West China Hospital
Inner Mongolia Baogang Hospital
Linyi People's Hospital
The First Affiliated Hospital of Zhengzhou University
Baotou Central Hospital
Information provided by (Responsible Party):
Yongjun Wang, 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.

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Drug: TNK-tPA Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Multicentre, prospective, randomization, open label, active and parallel control
Masking: Single (Outcomes Assessor)
Masking Description: open to patient, medical cares, and investigators, but blind to outcome evaluators
Primary Purpose: Treatment
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
Actual Study Start Date : May 12, 2018
Actual Primary Completion Date : May 30, 2020
Actual Study Completion Date : July 10, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ischemic Stroke

Arm Intervention/treatment
Experimental: Group 1 (rhTNK-tPA 0.10 mg/kg)
Dissolve 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.
Drug: TNK-tPA
Experimental arms for low, middle, and high dosing; and active control arm for the standard protocol
Other Name: rtPA

Experimental: Group 2 (rhTNK-tPA 0.25 mg/kg)
Dissolve 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.
Drug: TNK-tPA
Experimental arms for low, middle, and high dosing; and active control arm for the standard protocol
Other Name: rtPA

Experimental: Group 3 (rhTNK-tPA 0.32 mg/kg)
Dissolve 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.
Drug: TNK-tPA
Experimental arms for low, middle, and high dosing; and active control arm for the standard protocol
Other Name: rtPA

Active Comparator: Group 4 (rt-PA 0.9 mg/kg)
10% 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.
Drug: TNK-tPA
Experimental arms for low, middle, and high dosing; and active control arm for the standard protocol
Other Name: rtPA




Primary Outcome Measures :
  1. National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 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 :
  1. Modified Rankin Scale (mRS) [ Time Frame: 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.

  2. National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 90 days ]
    Neurological impairment defined as change of NIHSS score at 90 days.

  3. Barthel(BI) [ Time Frame: 90 days ]
    Global function of daily living defined as BI ≥ 95 at 90 days.

  4. EQ-5D [ Time Frame: 90 days ]
    Quality of life measured by EQ-5D scale.


Other Outcome Measures:
  1. Symptomatic intracranial hemorrhage(sICH) [ Time Frame: 36 hours ]
    Proportion of subjects with symptomatic intracranial hemorrhage (sICH) at 36 hours.

  2. Death [ Time Frame: 90 days ]
    Overall mortality rate at 90 days.

  3. Asymptomatic intracranial hemorrhage [ Time Frame: 90 days ]
    Proportion of patients with asymptomatic intracranial hemorrhage at 90 days.

  4. Hemorrhage in other parts [ Time Frame: 90 days ]
    The proportion of patients with other bleeding events was defined by GUSTO bleeding at 90 days.

  5. AE/SAE [ Time Frame: 90 days ]
    Proportion of patients with adverse events / severe adverse events at 90 days.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 .

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04676659


Locations
Show Show 24 study locations
Sponsors and Collaborators
Beijing Tiantan Hospital
Guangzhou Recomgen Biotech Co., Ltd.
The First Hospital Of Qiqihar
Hebei Medical University Third Hospital
Yantai Yuhuangding Hospital
Fudan University
First Affiliated Hospital of Jinan University
The First Hospital of Jilin University
Huashan Hospital
West China Hospital
Inner Mongolia Baogang Hospital
Linyi People's Hospital
The First Affiliated Hospital of Zhengzhou University
Baotou Central Hospital
Investigators
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Study Director: Meng Wang, MD,ph.D IRB of Beijing Tiantan Hospital,Capital Medical University
Publications of Results:
Carlos A Monlina,Marc Ribo,Marta Rubiera,et al.TNK Induces Faster MCA Recanalization and Leads to Better Short- and Long-term Clinical Outcome Than Native tPA.The TNK-tPA Reperfusion Stroke Study.Stroke2008,39:527 Abstract141.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Yongjun Wang, Vice President of Beijing Tiantan Hospital, Capital Medical University, Director of Neurology Center, Beijing Tiantan Hospital
ClinicalTrials.gov Identifier: NCT04676659    
Other Study ID Numbers: MK02-2016-01
First Posted: December 21, 2020    Key Record Dates
Last Update Posted: December 21, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yongjun Wang, Beijing Tiantan Hospital:
rhTNK-tPA
acute
stroke
phaseII
Acute Ischemic Stroke
rt-PA
Additional relevant MeSH terms:
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Stroke
Ischemic Stroke
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Tenecteplase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action