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THROMBOLYSISPhase 3TIMELESSNCT03785678

Tenecteplase in Stroke Patients Between 4.5 and 24 Hours

A Phase 3 study testing Tenecteplase in people with THROMBOLYSIS, run by Genentech, Inc. at 97 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

This study will evaluate the efficacy and safety of tenecteplase compared with placebo in participants with acute ischemic stroke (AIS). All participants will receive standard-of-care therapy according to AmericanHeart Association/American Stroke Association clinical guidelines (2018). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
THROMBOLYSIS
What is being tested?
Tenecteplase
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
458 participants
Where
97 sitesin 2 countries
Study dates
2 Mar 2019to 28 Feb 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patient/legally authorized representative has signed the Informed Consent Form
  • Age >= 18 years
  • AIS symptom onset within 4.5 to 24 hours Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the ICA, M1, or M2 vessels
  • Functionally independent (mRS 0-2) prior to stroke onset
  • Baseline NIHSS >=5 and that remains >=5 immediately prior to randomization
  • Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) by magnetic resonance angiography (MRA) or computed tomography angiography (CTA) AND target mismatch profile on CT perfusion or MR perfusion (ischemic core volume <70 mL, mismatch ratio is >=1.8 and mismatch volume is >= 15 mL)
Show all 12Show fewer
  • The mismatch volume is determined by FDA-approved imaging software in real time based on the difference between the ischemic core lesion volume and the Tmax>6s lesion volume. If both a CT perfusion and a multimodal MRI scan are performed prior to enrollment, the later of the 2 scans is assessed to determine eligibility. Only an intracranial MRA is required for patients screened with MRA; cervical MRA is not required. Cervical and intracranial CTA are typically obtained simultaneously in patients screened with CTA, but only the intracranial CTA is required for enrollment.
  • Alternative neuroimaging:
  • If CTA (or MRA) is technically inadequate: Tmax>6s perfusion deficit consistent with an ICA or M1, M2 occlusion AND target mismatch profile (ischemic core volume <70 mL, mismatch ratio >= 1.8 and mismatch volume >= 15 mL as determined by RAPID software)
  • If magnetic resonance perfusion (MRP) is technically inadequate: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI) AND diffusion-weighted imaging (DWI) lesion volume <=25 mL for an M1 or ICA occlusion and =<15 mL for an M2 occlusion
  • If CTP is technically inadequate: patient can be screened with MRI and randomized if neuroimaging criteria are met.
  • Ability to comply with the study protocol, in the investigator's judgment

Who cannot join

  • General
  • Current participation in another investigational drug or device study
  • Active internal bleeding
  • Known hypersensitivity or allergy to any ingredients of tenecteplase
  • Known bleeding diathesis
  • Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR >1.7
Show all 28Show fewer
  • Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
  • Pregnant
  • Intracranial neoplasm (except small meningioma), arteriovenous malformation, or aneurysm
  • Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
  • Severe, uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure > 110 mmHg)
  • For participants with suspected coagulopathy, platelet count must be checked prior to randomization and participant is excluded if baseline platelet count <100,000/microL
  • Baseline blood glucose >400 mg/dL (22.20 mmol/L)
  • Baseline blood glucose <50 mg/dL needs to be normalized prior to randomization
  • Clot retrieval attempted using a neurothrombectomy device prior to randomization
  • Intracranial or intraspinal surgery or trauma within 2 months
  • Treatment with a thrombolytic within the last 3 months prior to randomization
  • Other serious, advanced, or terminal illness (investigator judgment) with life expectancy less than 6 months
  • Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluations
  • History of cerebrovascular accident in the last 90 days
  • Presumed septic embolus; suspicion of bacterial endocarditis
  • Any other condition that, in the opinion of the investigator, precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was to be performed
  • Imaging
  • Unable to undergo a contrast brain perfusion scan with either MRI or CT
  • Extensive early ischemic change (hypodensity) on non-contrast CT estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria)
  • Significant mass effect
  • Acute symptomatic arterial occlusions in more than one vascular territory confirmed on CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)
  • Evidence of intracranial tumor (except small meningioma) acute intracranial hemorrhage, neoplasm, or arteriovenous malformation

Trial locations and contacts

97 sites in 2 countries.

97 sites in 2 countries

United States94 sites

  • Kaiser Permanente - Anaheim (E. La Palma)

    Anaheim, California, 92806

  • Univ of Michigan Medical Ctr

    Ann Arbor, Michigan, 48109-0718

  • Mission Hospitals Inc

    Asheville, North Carolina, 28803

  • Dell Seton Medical center at the University of Texas

    Austin, Texas, 78701

  • Seton Medical Center Austin

    Austin, Texas, 78705

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Johns Hopkins

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-3300

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Valley Baptist Medical Center-Brownsville

    Brownsville, Texas, 78520

  • Buffalo General Medical Center

    Buffalo, New York, 14203

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • University of Virginia

    Charlottesville, Virginia, 22906

  • Chattanooga Center for Neurologic Research

    Chattanooga, Tennessee, 37404

  • Northwestern University

    Chicago, Illinois, 60611

  • Univ of Cincinnati

    Cincinnati, Ohio, 45219

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Henry Ford Macomb Hospital - Clinton Township

    Clinton Township, Michigan, 48038

  • Riverside Methodist Hospital; Cancer Services

    Columbus, Ohio, 43214-1419

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Doctors Hospital

    Columbus, Ohio, 43228

  • John Muir Health, Concord Medical Center

    Concord, California, 94520

  • Baptist Health Corbin

    Corbin, Kentucky, 40701

  • Baylor University Medical Center

    Dallas, Texas, 75231

  • Sutter Davis Hospital

    Davis, California, 95616

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • St. Catherine Hospital

    East Chicago, Indiana, 46312

  • Fairview Southdale

    Edina, Minnesota, 55435

  • JFK Neuroscience Institute

    Edison, New Jersey, 08820

  • McLaren Flint

    Flint, Michigan, 48532

  • Kaiser Permanente - Fontana

    Fontana, California, 92335

  • University of Florida Health at Shands

    Gainesville, Florida, 32608

  • Adventist Health Glendale

    Glendale, California, 91206

  • Spectrum Health Hospitals

    Grand Rapids, Michigan, 49503

  • Guilford Neurologic Research

    Greensboro, North Carolina, 27405

  • Kaiser Permanente South Bay Medical Center

    Harbor City, California, 90710

  • Valley Baptist Medical Center

    Harlingen, Texas, 78550

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • St. Mary Medical Center

    Hobart, Indiana, 46432

  • The Queen's Medical Center

    Honolulu, Hawaii, 96813

  • University of Texas at Houston; Neurology

    Houston, Texas, 77030

  • Baptist Medical Center - Jacksonville

    Jacksonville, Florida, 32207-8202

  • Baptist Medical Center-South

    Jacksonville, Florida, 32258

  • Uni of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Ascension Seton Hays

    Kyle, Texas, 78640

  • UCSD Medical Center - La Jolla

    La Jolla, California, 92037

  • Baptist Health Lexington

    Lexington, Kentucky, 40503

  • Kaiser Permanente Los Angeles

    Los Angeles, California, 90027

  • University of Southern California Medical Center

    Los Angeles, California, 90033

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Cedars-Sinai Marina Del Rey Hospital

    Marina del Rey, California, 90292

  • Banner Desert Medical Center

    Mesa, Arizona, 85202

  • Jackson Memorial Hospital

    Miami, Florida, 33136

  • U of Minnesota MedCtr Fairview

    Minneapolis, Minnesota, 55455

  • ProMedica Monroe Regional Hospital

    Monroe, Michigan, 48162

  • UPMC East Hospital

    Monroeville, Pennsylvania, 15146

  • Community Hospital

    Munster, Indiana, 46321

  • Saint Thomas Rutherford Hospital

    Murfreesboro, Tennessee, 37129

  • Saint Thomas Health

    Nashville, Tennessee, 37205

  • Saint Thomas Midtown Hospital

    Nashville, Tennessee, 37232

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Columbia University Medical Center

    New York, New York, 10032

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • Kaiser Permanente - Ontario

    Ontario, California, 91761

  • Stanford University Medical Center

    Palo Alto, California, 94304

  • Advocate Lutheran General Hospital

    Park Ridge, Illinois, 60068

  • Penn Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

  • Uni of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • UPMC Mercy

    Pittsburgh, Pennsylvania, 15219

  • UPMC Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • Providence Portland Medical Center

    Portland, Oregon, 97213

  • Adventist Health Portland

    Portland, Oregon, 97216

  • Providence Saint Vincent's Medical Center

    Portland, Oregon, 97225

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Sutter Roseville Medical Center

    Roseville, California, 95661

  • Ascension Seton Williamson

    Round Rock, Texas, 78665

  • Sutter Medical Group, Neurology

    Sacramento, California, 95816

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCSD - Hillcrest; Hillcrest Medical Center

    San Diego, California, 92103

  • CPMC - Van Ness Campus

    San Francisco, California, 94109

  • CPMC - Davies Campus

    San Francisco, California, 94114

  • Sanford Neurology Clinic

    Sioux Falls, South Dakota, 57104

  • Washington University

    St Louis, Missouri, 63128

  • Atlantic Health System - Overlook Medical Center

    Summit, New Jersey, 07901

  • ProMedica Toledo Hospital

    Toledo, Ohio, 43606

  • Torrance Memorial Medical Center

    Torrance, California, 90505

  • Capital Health Regional Medical Center

    Trenton, New Jersey, 08638

  • Ascension St. John

    Tulsa, Oklahoma, 74104

  • John Muir Medical Center-Walnut Creek

    Walnut Creek, California, 94598

  • Sanford Worthington Medical Center

    Worthington, Minnesota, 56187

Other trials in United States

Canada3 sites

  • Uni of Alberta

    Edmonton, Alberta, T6G 2G3

  • Hamilton General Hospital; Pharmacy

    Hamilton, Ontario, L8L 2X2

  • Montreal Neurological Inst; Clinical Research Unit

    Montreal, Quebec, H3A 2B4

Other trials in Canada

About this study

Official title: A Phase III, Prospective, Double-blind, Randomized, Placebo-controlled Trial of Thrombolysis in Imaging-eligible, Late-window Patients to Assess the Efficacy and Safety of Tenecteplase (TIMELESS)

This study will evaluate the efficacy and safety of tenecteplase compared with placebo in participants with acute ischemic stroke (AIS).

All participants will receive standard-of-care therapy according to AmericanHeart Association/American Stroke Association clinical guidelines (2018). To determine eligibility for randomization, all participants will undergo multimodal CT or MRI at baseline. Only participants with a vessel occlusion (ICA or MCA M1/M2) and penumbral tissue will be randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in all participants at Day 90.

Conditions
THROMBOLYSIS
Being tested
Tenecteplase, Placebo

What participants receive

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

  • TenecteplaseBiological

    The investigational medicinal product (IMP) for this study is tenecteplase. The recommended total dose for this study is weight-based with 0.25 mg of tenecteplase per kg, not exceeding a maximum dose of 25 mg. A single bolus dose should be administered over 5 seconds based on patient weight.

  • PlaceboOther

    Placebo is being used as the comparator since a thrombolytic is only FDA-approved in the United States for use out to 3 hours, and the standard of care guidelines support use out to 4.5 hours.

Study groups in NCT03785678
Study groupRoleWhat they receive
TenecteplaseExperimentalPatients in this arm will receive Tenecteplase (0.25 mg/kg, maximum 25 mg) administered as a single bolus injection over 5 seconds.
Receives: Biological: Tenecteplase
PlaceboPlacebo comparatorPatients in this arm will receive placebo administered as a single bolus injection over 5 seconds.
Receives: Other: Placebo

What is being measured

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

  1. Ordinal Modified Rankin Scale (mRS) Score at Day 90

    The the modified Rankin score (mRS) is a 6-point scale commonly used to assess disability due to stroke, with higher values indicating worse outcomes.

    0 = No symptoms

    1. = No significant disability
    2. = Slight disability
    3. = Moderate disability
    4. = Moderately severe disability
    5. = Severe disability
    6. = Death

    Measured: Day 90

Secondary outcomes (10)

  1. Proportion of Patients With Functional Independence at Day 90

    Functional independence, was defined as an mRS of 0-2 (no symptoms to mild symptoms), at Day 90.

    Measured: Day 90

  2. Proportion of Patients With Recanalization at 24 Hours Post-randomization

    This endpoint measured complete or partial recanalization (restored blood flow) on CT angiography (CTA)/magnetic resonance angiography (MRA) post-randomization, defined as complete or partial recanalization on CT angiography (CTA)/magnetic resonance angiography (MRA).

    Measured: Day 2

  3. Proportion of Patients With Reperfusion at 24 Hours Post-randomization

    This endpoint was defined by the proportion of participants with reperfusion (the restoration of blood flow to an organ or tissue after having been blocked) at 24 hours post-randomization, defined as > 90% reduction in Tmax > 6s lesion volume.

    Measured: Day 2

  4. Proportion of Patients With Angiographic Reperfusion at Completion of Angiographic Procedure

    Angiographic reperfusion was evaluated using the modified Thrombolysis in Cerebral Infarction (TICI) Scale:

    0: No perfusion or anterograde flow beyond site of occlusion.

    1. Contrast passes the area of occlusion but fails to opacify the entire cerebral bed distal to the obstruction during angiographic run.
    2. Partial perfusion wherein the contrast passes the occlusion and opacifies the distal arterial bed but rate of entry or clearance from the bed is slower than non-involved territories 2A: < 50% of territory visualized 2B: ≥ 50% of territory is visualized 2C: Near complete perfusion except for slow flow in a few distal cortical vessels or presence of small distal cortical emboli
    3. Complete reperfusion with normal filling.

    Measured: Day 1

  5. Median NIHSS Score at Day 90

    The National Institutes of Health Stroke Score (NIHSS) is a 15-item scale that measures neurological deficit in acute stroke patients. Each item is ranked using a 3-, 4-, or 5-point scale, including allowances for items that cannot be scored due to the patient's condition, with higher scores indicating more severe deficit. Total scores range from 0-42, with higher scores indicating more severe deficits.

    Measured: Day 90

  6. Proportion of Patients With a Barthel Index (BI) Score ≥ 95 at Day 90

    The Barthel Index (BI) is a 10-item ordinal scale used to measure performance in activities of daily living (ADL) and mobility. The BI scoring range is from 0-100, with lower scores representing greater dependency.

    Measured: Day 90

  7. Proportion of Patients With Good Recovery Based on the Glasgow Outcome Scale (GOS) at Day 90

    The Glasgow Outcome Scale (GOS) is a scale used to assess recovery of participants with brain damage. The scale has 5 categories:

    1. = Death
    2. = Persistent vegetative state
    3. = Severe disability
    4. = Moderate disability
    5. = Good recovery

    The GOS was re-scaled from observed data. For this measure, 1 = good recovery and 5 = death.

    Measured: Day 90

  8. Incidence of Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours

    Measured: Within 36 hours (Day 2) of treatment

  9. Mortality Rate up to Day 30 and Day 90

    Measured: Day 30 and Day 90

  10. Proportion of Patients With Parenchymal Hematoma Type 2 (PH2) at the 72-96 Hour Visit

    Measured: Day 3

Timeline

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

  1. First posted24 Dec 2018
  2. Study start2 Mar 2019
  3. Primary completion28 Feb 2023
  4. Study completion28 Feb 2023

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
458 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03785678
Sponsor's protocol ID
ML40787
Acronym
TIMELESS
Status last verified
May 2024
First submitted
19 Dec 2018
Last updated
22 May 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Albers GW, Jumaa M, Purdon B, Zaidi SF, Streib C, Shuaib A, Sangha N, Kim M, Froehler MT, Schwartz NE, Clark WM, Kircher CE, Yang M, Massaro L, Lu XY, Rippon GA, Broderick JP, Butcher K, Lansberg MG, Liebeskind DS, Nouh A, Schwamm LH, Campbell BCV; TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. N Engl J Med. 2024 Feb 22;390(8):701-711. doi: 10.1056/NEJMoa2310392. Epub 2024 Feb 8.

    PubMed 38329148

  • Zachrison KS, Amati V, Schwamm LH, Yan Z, Nielsen V, Christie A, Reeves MJ, Sauser JP, Lomi A, Onnela JP. Influence of Hospital Characteristics on Hospital Transfer Destinations for Patients With Stroke. Circ Cardiovasc Qual Outcomes. 2022 May;15(5):e008269. doi: 10.1161/CIRCOUTCOMES.121.008269. Epub 2022 Apr 4.

    PubMed 35369714

  • Albers GW, Campbell BC, Lansberg MG, Broderick J, Butcher K, Froehler MT, Schwamm LH, Nouh AM, Liebeskind DS, Toy F, Yang M, Massaro L, Schoeffler M, Purdon B. A Phase III, prospective, double-blind, randomized, placebo-controlled trial of thrombolysis in imaging-eligible, late-window patients to assess the efficacy and safety of tenecteplase (TIMELESS): Rationale and design. Int J Stroke. 2023 Feb;18(2):237-241. doi: 10.1177/17474930221088400. Epub 2022 Apr 1.

    PubMed 35262424

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tenecteplase in people with THROMBOLYSIS, run by Genentech, Inc. at 97 sites in 2 countries.

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 12 inclusion and 28 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 22 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 97 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Ordinal Modified Rankin Scale (mRS) Score at Day 90 (time frame: Day 90). 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 NCT03785678, which also lists 3 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 22 May 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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