Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events(TRACE)

NCT04676659 | Completed Phase 2 DMC

• 1 other identifier: MK02-2016-01
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 24

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.

Conditions

Acute Ischemic Stroke

Keywords

rhTNK-tPA; acute; stroke; phaseII; Acute Ischemic Stroke; rt-PA

Outcome Measures

Primary Outcomes (1)

• National Institutes of Health Stroke Scale (NIHSS)

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

  14 days

Secondary Outcomes (4)

• Modified Rankin Scale (mRS)

  90 days

• National Institutes of Health Stroke Scale (NIHSS)

  90 days

• Barthel(BI)

  90 days

• EQ-5D

  90 days

Other Outcomes (5)

• Symptomatic intracranial hemorrhage(sICH)

  36 hours

• Death

  90 days

• Asymptomatic intracranial hemorrhage

  90 days

Study Arms (4)

Group 1 (rhTNK-tPA 0.10 mg/kg)

EXPERIMENTAL

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

Group 2 (rhTNK-tPA 0.25 mg/kg)

EXPERIMENTAL

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

Group 3 (rhTNK-tPA 0.32 mg/kg)

EXPERIMENTAL

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

Group 4 (rt-PA 0.9 mg/kg)

ACTIVE COMPARATOR

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

Interventions

TNK-tPA DRUG

Experimental arms for low, middle, and high dosing; and active control arm for the standard protocol

Also known as: rtPA

Group 1 (rhTNK-tPA 0.10 mg/kg); Group 2 (rhTNK-tPA 0.25 mg/kg); Group 3 (rhTNK-tPA 0.32 mg/kg); Group 4 (rt-PA 0.9 mg/kg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 18 years.
• Time from onset to treatment \< 3 hours; the time symptoms start is defined as "the last moment they appear normal".
• 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.
• mRS \> 2 at the first onset or prior onset.
• Baseline NIHSS score is \> 4 and \< 26.
• Signed informed consent.

You may not qualify if:

• Absolute contraindications:
• 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 )
• 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 ).
• 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.
• Have been enrolled in rhTNK-tPA in pre-study or participated in other clinical trials within 3 months prior to screening.
• Lactating women, or childbearing women who do not use effective contraception.
• Known allergy to rhTNK-tPA and/or rt-PA or relevant excipients.
• The researchers judged that not suitable to participate in this study or participate in this study may lead to greater risk for patients ;
• Can not comply with the test program or follow-up requirements .

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.: collaborator
• The First Hospital Of Qiqihar: collaborator
• Hebei Medical University Third Hospital: collaborator
• Yantai Yuhuangding Hospital: collaborator
• Fudan University: collaborator
• First Affiliated Hospital of Jinan University: collaborator
• The First Hospital of Jilin University: collaborator
• Huashan Hospital: collaborator
• West China Hospital: collaborator
• Inner Mongolia Baogang Hospital: collaborator
• Linyi People's Hospital: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• Baotou Central Hospital: collaborator

Study Sites (24)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Location

The Ninth People's Hospital of Chongqing

Chongqing, Chongqing Municipality, China

Location

First Affiliated Hospital of Jinan University

Guangzhou, Guangdong, China

Location

ShenZhen Hospital ,Beijing University

Shenzhen, Guangdong, China

Location

Affiliated Hosptial to GuiZhou Medical University

Guiyang, Guizhou, China

Location

HaiNan Provincial People's Hospital

Haikou, Hainan, China

Location

Hebei Medical University Third Hospital

Shijiazhuang, Hebei, 050051, China

Location

Tangshan Workers' Hospital

Tangshan, Hebei, China

Location

The First Hospital Of Qiqihar

Qiqihar, Heilongjiang, China

Location

Luoyang First People's Hosptical

Luoyang, Henan, 471000, China

Location

1st Hospital Affiliated to Zhengzhou University

Zhengzhou, Henan, China

Location

ChangSha 1st Municipal Hospital

Changsha, Hunan, China

Location

Baotou Central Hospital

Baotou, Inner Mongolia, China

Location

Inner Mongolia BaoGang Hospital

Baotou, Inner Mongolia, China

Location

Huai'an Second People's Hospital

Huai'an, Jiangsu, China

Location

First Hospital of Jilin University

Changchun, Jilin, China

Location

Meihekou Central Hospital

Tonghua, Jilin, 135000, China

Location

First People 's Hospital Of Shenyang

Shenyang, Liaoning, China

Location

General Hospital of Northern War Zone , PLA

Shenyang, Liaoning, China

Location

Linyi People's Hospital

Linyi, Shandong, China

Location

Yantai Yuhuangding Hospital

Yantai, Shandong, China

Location

HuaShan Hospital Affiliated to FuDan University

Shanghai, Shanghai Municipality, China

Location

ZhongShan Hospital ,FuDan University

Shanghai, Shanghai Municipality, China

Location

SiChuan University HuaXi Hospital

Chengdu, Sichuan, China

Location

Related Publications (19)

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• 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.

  RESULT

• Haley EC Jr, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL, Fanale C, Libman R, Kwiatkowski TG, Llinas RH, Levine SR, Johnston KC, Buchsbaum R, Levy G, Levin B; Tenecteplase in Stroke Investigators. Phase IIB/III trial of tenecteplase in acute ischemic stroke: results of a prematurely terminated randomized clinical trial. Stroke. 2010 Apr;41(4):707-11. doi: 10.1161/STROKEAHA.109.572040. Epub 2010 Feb 25.

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  PMID: 22435369 RESULT

• Coutts SB, Dubuc V, Mandzia J, Kenney C, Demchuk AM, Smith EE, Subramaniam S, Goyal M, Patil S, Menon BK, Barber PA, Dowlatshahi D, Field T, Asdaghi N, Camden MC, Hill MD; TEMPO-1 Investigators. Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion. Stroke. 2015 Mar;46(3):769-74. doi: 10.1161/STROKEAHA.114.008504. Epub 2015 Feb 12.

  PMID: 25677596 RESULT

• Li S, Pan Y, Wang Z, Liang Z, Chen H, Wang D, Sui Y, Zhao X, Wang Y, Du W, Zheng H, Wang Y. Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study. Stroke Vasc Neurol. 2022 Feb;7(1):47-53. doi: 10.1136/svn-2021-000978. Epub 2021 Aug 24.

  PMID: 34429364 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

TNK-tissue plasminogen activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Meng Wang, MD,ph.D

  IRB of Beijing Tiantan Hospital,Capital Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: open to patient, medical cares, and investigators, but blind to outcome evaluators
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital, Capital Medical University, Director of Neurology Center

Model Details: Multicentre, prospective, randomization, open label, active and parallel control

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: December 21, 2020
• Study Start: May 12, 2018
• Primary Completion: May 30, 2020
• Study Completion: July 10, 2020
• Last Updated: December 21, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (24)