Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events(TRACE)

December 18, 2020 updated by: Yongjun Wang, Beijing Tiantan Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

240

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China
        • Beijing Tiantan Hospital, Capital Medical University
    • Chongqing
      • Chongqing, Chongqing, China
        • The Ninth People'S Hospital of Chongqing
    • Guangdong
      • Guangzhou, Guangdong, China
        • First Affiliated Hospital of Jinan University
      • Shenzhen, Guangdong, China
        • ShenZhen Hospital ,Beijing University
    • Guizhou
      • Guiyang, Guizhou, China
        • Affiliated Hosptial to GuiZhou Medical University
    • Hainan
      • Haikou, Hainan, China
        • Hainan Provincial People's Hospital
    • Hebei
      • Shijiazhuang, Hebei, China, 050051
        • Hebei medical university third hospital
      • Tangshan, Hebei, China
        • Tangshan Workers' Hospital
    • Heilongjiang
      • Qiqihar, Heilongjiang, China
        • The First Hospital of Qiqihar
    • Henan
      • Luoyang, Henan, China, 471000
        • Luoyang First People's Hosptical
      • Zhengzhou, Henan, China
        • 1st Hospital Affiliated to Zhengzhou University
    • Hunan
      • Changsha, Hunan, China
        • ChangSha 1st Municipal Hospital
    • Inner Mongolia
      • Baotou, Inner Mongolia, China
        • Inner Mongolia Baogang Hospital
      • Baotou, Inner Mongolia, China
        • Baotou Central Hospital
    • Jiangsu
      • Huai'an, Jiangsu, China
        • Huai'an Second People's Hospital
    • Jilin
      • Chang chun, Jilin, China
        • First Hospital of Jilin University
      • Tonghua, Jilin, China, 135000
        • Meihekou Central Hospital
    • Liaoning
      • Shenyang, Liaoning, China
        • First People 's Hospital Of Shenyang
      • Shenyang, Liaoning, China
        • General Hospital of Northern War Zone , PLA
    • Shandong
      • Linyi, Shandong, China
        • Linyi People's Hospital
      • Yantai, Shandong, China
        • Yantai Yuhuangding Hospital
    • Shanghai
      • Shanghai, Shanghai, China
        • Huashan Hospital affiliated to Fudan University
      • Shanghai, Shanghai, China
        • Zhongshan Hospital ,Fudan University
    • Sichuan
      • Chengdu, Sichuan, China
        • Sichuan University Huaxi Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 .

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • rtPA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EQ-5D
Time Frame: 90 days
Quality of life measured by EQ-5D scale.
90 days
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.
90 days
National Institutes of Health Stroke Scale (NIHSS)
Time Frame: 90 days
Neurological impairment defined as change of NIHSS score at 90 days.
90 days
Barthel(BI)
Time Frame: 90 days
Global function of daily living defined as BI ≥ 95 at 90 days.
90 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Symptomatic intracranial hemorrhage(sICH)
Time Frame: 36 hours
Proportion of subjects with symptomatic intracranial hemorrhage (sICH) at 36 hours.
36 hours
Death
Time Frame: 90 days
Overall mortality rate at 90 days.
90 days
Asymptomatic intracranial hemorrhage
Time Frame: 90 days
Proportion of patients with asymptomatic intracranial hemorrhage at 90 days.
90 days
Hemorrhage in other parts
Time Frame: 90 days
The proportion of patients with other bleeding events was defined by GUSTO bleeding at 90 days.
90 days
AE/SAE
Time Frame: 90 days
Proportion of patients with adverse events / severe adverse events at 90 days.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tiantan Hospital

Collaborators

Fudan University
Huashan Hospital
West China Hospital
The First Affiliated Hospital of Zhengzhou University
The First Hospital of Jilin University
First Affiliated Hospital of Jinan University
Hebei Medical University Third Hospital
Yantai Yuhuangding Hospital
Linyi People's Hospital
Baotou Central Hospital
Guangzhou Recomgen Biotech Co., Ltd.
The First Hospital Of Qiqihar
Inner Mongolia Baogang Hospital

Investigators

  • Study Director: Meng Wang, MD,ph.D, IRB of Beijing Tiantan Hospital,Capital Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 12, 2018

Primary Completion (Actual)

May 30, 2020

Study Completion (Actual)

July 10, 2020

Study Registration Dates

First Submitted

July 27, 2020

First Submitted That Met QC Criteria

December 18, 2020

First Posted (Actual)

December 21, 2020

Study Record Updates

Last Update Posted (Actual)

December 21, 2020

Last Update Submitted That Met QC Criteria

December 18, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MK02-2016-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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