Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 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) - 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

Exclusion Criteria

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 - 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Tenecteplase
Patients in this arm will receive Tenecteplase (0.25 mg/kg, maximum 25 mg) administered as a single bolus injection over 5 seconds.
  • Biological: Tenecteplase
    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.
Placebo Comparator
Placebo
Patients in this arm will receive placebo administered as a single bolus injection over 5 seconds.
  • Other: Placebo
    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.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294-3300

Banner Desert Medical Center
Mesa, Arizona 85202

University of Arkansas For Medical Sciences
Little Rock, Arkansas 72205

Adventist Health Glendale
Glendale, California 91206

UCSD Medical Center - La Jolla
La Jolla, California 92037

University of Southern California Medical Center
Los Angeles, California 90033

Cedars-Sinai Medical Center
Los Angeles, California 90048

Stanford University Medical Center
Palo Alto, California 94304

Sutter Medical Group, Neurology
Sacramento, California 95816

CPMC - Van Ness Campus
San Francisco, California 94109

John Muir Medical Center-Walnut Creek
Walnut Creek, California 94598

Hartford Hospital
Hartford, Connecticut 06102

University of Florida Health at Shands
Gainesville, Florida 32608

Baptist Medical Center - Jacksonville
Jacksonville, Florida 32207-8202

Jackson Memorial Hospital
Miami, Florida 33136

The Queen's Medical Center
Honolulu, Hawaii 96813

Northwestern University
Chicago, Illinois 60611

Advocate Lutheran General Hospital
Park Ridge, Illinois 60068

Uni of Kansas Medical Center
Kansas City, Kansas 66160

Baptist Health Lexington
Lexington, Kentucky 40503

Sinai Hospital of Baltimore
Baltimore, Maryland 21215

Johns Hopkins
Baltimore, Maryland 21287

Massachusetts General Hospital
Boston, Massachusetts 02114

Univ of Michigan Medical Ctr
Ann Arbor, Michigan 48109-0718

Henry Ford Hospital
Detroit, Michigan 48202

McLaren Flint
Flint, Michigan 48532

Spectrum Health Hospitals
Grand Rapids, Michigan 49503

Fairview Southdale
Edina, Minnesota 55435

U of Minnesota MedCtr Fairview
Minneapolis, Minnesota 55455

JFK Neuroscience Institute
Edison, New Jersey 08820

Hackensack University Medical Center
Hackensack, New Jersey 07601

Columbia University Medical Center
New York, New York 10032

Guilford Neurologic Research
Greensboro, North Carolina 27405

Univ of Cincinnati
Cincinnati, Ohio 45219

Cleveland Clinic
Cleveland, Ohio 44195

Riverside Methodist Hospital; Cancer Services
Columbus, Ohio 43214-1419

ProMedica Toledo Hospital
Toledo, Ohio 43606

Ascension St. John
Tulsa, Oklahoma 74104

Providence Portland Medical Center
Portland, Oregon 97213

Providence Saint Vincent's Medical Center
Portland, Oregon 97225

Uni of Pennsylvania
Philadelphia, Pennsylvania 19104

University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15213

Rhode Island Hospital
Providence, Rhode Island 02903

Saint Thomas Rutherford Hospital
Murfreesboro, Tennessee 37129

Valley Baptist Medical Center
Harlingen, Texas 78550

University of Texas at Houston; Neurology
Houston, Texas 77030

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229

University of Virginia
Charlottesville, Virginia 22906

More Details

NCT ID
NCT03785678
Status
Recruiting
Sponsor
Genentech, Inc.

Study Contact

Reference Study ID Number: ML40787 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.