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Acute Ischemic StrokePhase 2NCT04676659

Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events(TRACE)

A Phase 2 study testing TNK-tPA in people with Acute Ischemic Stroke, run by Beijing Tiantan Hospital at 24 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Ischemic Stroke
What is being tested?
TNK-tPA
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
240 participants
Where
24 sitesChina
Study dates
12 May 2018to 10 Jul 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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 )
  • 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.
  • 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.
Show all 9Show fewer
  • 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 .

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

China24 sites

  • Baotou Central Hospital

    Baotou, Inner Mongolia

  • Inner Mongolia BaoGang Hospital

    Baotou, Inner Mongolia

  • Beijing Tiantan Hospital, Capital Medical University

    Beijing, Beijing Municipality

  • First Hospital of Jilin University

    Changchun, Jilin

  • ChangSha 1st Municipal Hospital

    Changsha, Hunan

  • SiChuan University HuaXi Hospital

    Chengdu, Sichuan

  • The Ninth People's Hospital of Chongqing

    Chongqing, Chongqing Municipality

  • First Affiliated Hospital of Jinan University

    Guangzhou, Guangdong

  • Affiliated Hosptial to GuiZhou Medical University

    Guiyang, Guizhou

  • HaiNan Provincial People's Hospital

    Haikou, Hainan

  • Huai'an Second People's Hospital

    Huai'an, Jiangsu

  • Linyi People's Hospital

    Linyi, Shandong

  • Luoyang First People's Hosptical

    Luoyang, Henan, 471000

  • The First Hospital Of Qiqihar

    Qiqihar, Heilongjiang

  • HuaShan Hospital Affiliated to FuDan University

    Shanghai, Shanghai Municipality

  • ZhongShan Hospital ,FuDan University

    Shanghai, Shanghai Municipality

  • First People 's Hospital Of Shenyang

    Shenyang, Liaoning

  • General Hospital of Northern War Zone , PLA

    Shenyang, Liaoning

  • ShenZhen Hospital ,Beijing University

    Shenzhen, Guangdong

  • Hebei Medical University Third Hospital

    Shijiazhuang, Hebei, 050051

  • Tangshan Workers' Hospital

    Tangshan, Hebei

  • Meihekou Central Hospital

    Tonghua, Jilin, 135000

  • Yantai Yuhuangding Hospital

    Yantai, Shandong

  • 1st Hospital Affiliated to Zhengzhou University

    Zhengzhou, Henan

Other trials in China

About this study

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

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.

Read the 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.

Being tested
TNK-tPA
Keywords
rhTNK-tPA, acute, stroke, phaseII, Acute Ischemic Stroke, rt-PA
Medical subject headings
Ischemic Stroke, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TNK-tPADrug

    Also called rtPA

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

Study groups in NCT04676659
Study groupRoleWhat they receive
Group 1 (rhTNK-tPA 0.10 mg/kg)ExperimentalDissolve 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.
Receives: Drug: TNK-tPA
Group 2 (rhTNK-tPA 0.25 mg/kg)ExperimentalDissolve 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.
Receives: Drug: TNK-tPA
Group 3 (rhTNK-tPA 0.32 mg/kg)ExperimentalDissolve 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.
Receives: Drug: TNK-tPA
Group 4 (rt-PA 0.9 mg/kg)Active comparator10% 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.
Receives: Drug: TNK-tPA

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 14 days

Secondary outcomes (4)

  1. Modified Rankin Scale (mRS)

    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.

    Measured: 90 days

  2. National Institutes of Health Stroke Scale (NIHSS)

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

    Measured: 90 days

  3. Barthel(BI)

    Global function of daily living defined as BI ≥ 95 at 90 days.

    Measured: 90 days

  4. EQ-5D

    Quality of life measured by EQ-5D scale.

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2020
  2. Study start12 May 2018
  3. Primary completion30 May 2020
  4. Study completion10 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicentre, prospective, randomization, open label, active and parallel control
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
240 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04676659
Sponsor's protocol ID
MK02-2016-01
Status last verified
Dec 2020
First submitted
27 Jul 2020
Last updated
21 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7;349(9066):1641-9.

    PubMed 9186381

  • Wang Z, Li J, Wang C, Yao X, Zhao X, Wang Y, Li H, Liu G, Wang A, Wang Y. Gender differences in 1-year clinical characteristics and outcomes after stroke: results from the China National Stroke Registry. PLoS One. 2013;8(2):e56459. doi: 10.1371/journal.pone.0056459. Epub 2013 Feb 13.

    PubMed 23418571

  • Wei JW, Heeley EL, Wang JG, Huang Y, Wong LK, Li Z, Heritier S, Arima H, Anderson CS; ChinaQUEST Investigators. Comparison of recovery patterns and prognostic indicators for ischemic and hemorrhagic stroke in China: the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) Registry study. Stroke. 2010 Sep;41(9):1877-83. doi: 10.1161/STROKEAHA.110.586909. Epub 2010 Jul 22.

    PubMed 20651267

  • Bandera E, Botteri M, Minelli C, Sutton A, Abrams KR, Latronico N. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke. 2006 May;37(5):1334-9. doi: 10.1161/01.STR.0000217418.29609.22. Epub 2006 Mar 30.

    PubMed 16574919

  • Donnan GA, Baron JC, Ma H, Davis SM. Penumbral selection of patients for trials of acute stroke therapy. Lancet Neurol. 2009 Mar;8(3):261-9. doi: 10.1016/S1474-4422(09)70041-9.

    PubMed 19233036

  • Macleod MR, Petersson J, Norrving B, Hacke W, Dirnagl U, Wagner M, Schwab S; European Hypothermia Stroke Research Workshop. Hypothermia for Stroke: call to action 2010. Int J Stroke. 2010 Dec;5(6):489-92. doi: 10.1111/j.1747-4949.2010.00520.x.

    PubMed 21086713

  • Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC, Davis SM, Donnan GA, Hacke W; ECASS, ATLANTIS, NINDS and EPITHET rt-PA Study Group; Allen K, Mau J, Meier D, del Zoppo G, De Silva DA, Butcher KS, Parsons MW, Barber PA, Levi C, Bladin C, Byrnes G. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 2010 May 15;375(9727):1695-703. doi: 10.1016/S0140-6736(10)60491-6.

    PubMed 20472172

  • Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.

    PubMed 18815396

  • Wahlgren N, Ahmed N, Davalos A, Hacke W, Millan M, Muir K, Roine RO, Toni D, Lees KR; SITS investigators. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008 Oct 11;372(9646):1303-9. doi: 10.1016/S0140-6736(08)61339-2. Epub 2008 Sep 12.

    PubMed 18790527

  • Davis SM, Donnan GA, Parsons MW, Levi C, Butcher KS, Peeters A, Barber PA, Bladin C, De Silva DA, Byrnes G, Chalk JB, Fink JN, Kimber TE, Schultz D, Hand PJ, Frayne J, Hankey G, Muir K, Gerraty R, Tress BM, Desmond PM; EPITHET investigators. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008 Apr;7(4):299-309. doi: 10.1016/S1474-4422(08)70044-9. Epub 2008 Feb 28.

    PubMed 18296121

  • Lees GJ. Pharmacology of AMPA/kainate receptor ligands and their therapeutic potential in neurological and psychiatric disorders. Drugs. 2000 Jan;59(1):33-78. doi: 10.2165/00003495-200059010-00004.

    PubMed 10718099

  • Davydov L, Cheng JW. Tenecteplase: a review. Clin Ther. 2001 Jul;23(7):982-97; discussion 981. doi: 10.1016/s0149-2918(01)80086-2.

    PubMed 11519775

  • Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, Ford I, Muir KW. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4):368-76. doi: 10.1016/S1474-4422(15)70017-7. Epub 2015 Feb 26.

    PubMed 25726502

  • Haley EC Jr, Lyden PD, Johnston KC, Hemmen TM; TNK in Stroke Investigators. A pilot dose-escalation safety study of tenecteplase in acute ischemic stroke. Stroke. 2005 Mar;36(3):607-12. doi: 10.1161/01.STR.0000154872.73240.e9. Epub 2005 Feb 3.

    PubMed 15692126

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TNK-tPA in people with Acute Ischemic Stroke, run by Beijing Tiantan Hospital at 24 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

National Institutes of Health Stroke Scale (NIHSS) (time frame: 14 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04676659, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2020.

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