Tenecteplase in Stroke Patients Between 4.5 and 24 Hours
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
- THROMBOLYSIS
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
Arm | Description | Assigned 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. |
|
Placebo Comparator Placebo |
Patients in this arm will receive placebo administered as a single bolus injection over 5 seconds. |
|
Recruiting Locations
Birmingham, Alabama 35294-3300
Mesa, Arizona 85202
Little Rock, Arkansas 72205
Glendale, California 91206
La Jolla, California 92037
Los Angeles, California 90033
Los Angeles, California 90048
Palo Alto, California 94304
Sacramento, California 95816
San Francisco, California 94109
Walnut Creek, California 94598
Hartford, Connecticut 06102
Gainesville, Florida 32608
Jacksonville, Florida 32207-8202
Miami, Florida 33136
Honolulu, Hawaii 96813
Chicago, Illinois 60611
Park Ridge, Illinois 60068
Kansas City, Kansas 66160
Lexington, Kentucky 40503
Baltimore, Maryland 21215
Baltimore, Maryland 21287
Boston, Massachusetts 02114
Ann Arbor, Michigan 48109-0718
Detroit, Michigan 48202
Flint, Michigan 48532
Grand Rapids, Michigan 49503
Edina, Minnesota 55435
Minneapolis, Minnesota 55455
Edison, New Jersey 08820
Hackensack, New Jersey 07601
New York, New York 10032
Greensboro, North Carolina 27405
Cincinnati, Ohio 45219
Cleveland, Ohio 44195
Columbus, Ohio 43214-1419
Toledo, Ohio 43606
Tulsa, Oklahoma 74104
Portland, Oregon 97213
Portland, Oregon 97225
Philadelphia, Pennsylvania 19104
Pittsburgh, Pennsylvania 15213
Providence, Rhode Island 02903
Murfreesboro, Tennessee 37129
Harlingen, Texas 78550
Houston, Texas 77030
San Antonio, Texas 78229
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