Tenecteplase in Stroke Patients Between 4.5 and 24 Hours
- Conditions
- THROMBOLYSIS
- Interventions
- Other: PlaceboBiological: Tenecteplase
- Registration Number
- NCT03785678
- Lead Sponsor
- Genentech, Inc.
- Brief 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). 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 458
- 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
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Patients in this arm will receive placebo administered as a single bolus injection over 5 seconds. Tenecteplase Tenecteplase Patients in this arm will receive Tenecteplase (0.25 mg/kg, maximum 25 mg) administered as a single bolus injection over 5 seconds.
- Primary Outcome Measures
Name Time Method Ordinal Modified Rankin Scale (mRS) Score at Day 90 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
- Secondary Outcome Measures
Name Time Method Median NIHSS Score at Day 90 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.
Proportion of Patients With Good Recovery Based on the Glasgow Outcome Scale (GOS) at Day 90 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.Mortality Rate up to Day 30 and Day 90 Day 30 and Day 90 Proportion of Patients With Reperfusion at 24 Hours Post-randomization Day 2 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.
Incidence of Symptomatic Intracranial Hemorrhage (sICH) Within 36 Hours Within 36 hours (Day 2) of treatment Proportion of Patients With Parenchymal Hematoma Type 2 (PH2) at the 72-96 Hour Visit Day 3 Proportion of Patients With Functional Independence at Day 90 Day 90 Functional independence, was defined as an mRS of 0-2 (no symptoms to mild symptoms), at Day 90.
Proportion of Patients With Recanalization at 24 Hours Post-randomization Day 2 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).
Proportion of Patients With Angiographic Reperfusion at Completion of Angiographic Procedure Day 1 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.Proportion of Patients With a Barthel Index (BI) Score ≥ 95 at Day 90 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.
Trial Locations
- Locations (97)
Kaiser Permanente Los Angeles
🇺🇸Los Angeles, California, United States
University of Southern California Medical Center
🇺🇸Los Angeles, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Grant Medical Center
🇺🇸Columbus, Ohio, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Ascension Seton Williamson
🇺🇸Round Rock, Texas, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Texas at Houston; Neurology
🇺🇸Houston, Texas, United States
UCSD - Hillcrest; Hillcrest Medical Center
🇺🇸San Diego, California, United States
Jackson Memorial Hospital
🇺🇸Miami, Florida, United States
Univ of Cincinnati
🇺🇸Cincinnati, Ohio, United States
CPMC - Van Ness Campus
🇺🇸San Francisco, California, United States
U of Minnesota MedCtr Fairview
🇺🇸Minneapolis, Minnesota, United States
Saint Thomas Health
🇺🇸Nashville, Tennessee, United States
Saint Thomas Midtown Hospital
🇺🇸Nashville, Tennessee, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Uni of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
JFK Neuroscience Institute
🇺🇸Edison, New Jersey, United States
Banner Desert Medical Center
🇺🇸Mesa, Arizona, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Chattanooga Center for Neurologic Research
🇺🇸Chattanooga, Tennessee, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Capital Health Regional Medical Center
🇺🇸Trenton, New Jersey, United States
Advocate Lutheran General Hospital
🇺🇸Park Ridge, Illinois, United States
Atlantic Health System - Overlook Medical Center
🇺🇸Summit, New Jersey, United States
Saint Thomas Rutherford Hospital
🇺🇸Murfreesboro, Tennessee, United States
Uni of Alberta
🇨🇦Edmonton, Alberta, Canada
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Adventist Health Portland
🇺🇸Portland, Oregon, United States
Providence Saint Vincent's Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Sutter Medical Group, Neurology
🇺🇸Sacramento, California, United States
Univ of Michigan Medical Ctr
🇺🇸Ann Arbor, Michigan, United States
Kaiser Permanente - Anaheim (E. La Palma)
🇺🇸Anaheim, California, United States
John Muir Health, Concord Medical Center
🇺🇸Concord, California, United States
Mills-Peninsula Medical Center
🇺🇸Burlingame, California, United States
Sutter Davis Hospital
🇺🇸Davis, California, United States
Kaiser Permanente - Fontana
🇺🇸Fontana, California, United States
Adventist Health Glendale
🇺🇸Glendale, California, United States
UCSD Medical Center - La Jolla
🇺🇸La Jolla, California, United States
Kaiser Permanente South Bay Medical Center
🇺🇸Harbor City, California, United States
Cedars-Sinai Marina Del Rey Hospital
🇺🇸Marina Del Rey, California, United States
Kaiser Permanente - Ontario
🇺🇸Ontario, California, United States
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Sutter Roseville Medical Center
🇺🇸Roseville, California, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
CPMC - Davies Campus
🇺🇸San Francisco, California, United States
John Muir Medical Center-Walnut Creek
🇺🇸Walnut Creek, California, United States
Baptist Medical Center - Jacksonville
🇺🇸Jacksonville, Florida, United States
Baptist Medical Center-South
🇺🇸Jacksonville, Florida, United States
St. Catherine Hospital
🇺🇸East Chicago, Indiana, United States
St. Mary Medical Center
🇺🇸Hobart, Indiana, United States
Community Hospital
🇺🇸Munster, Indiana, United States
Baptist Health Corbin
🇺🇸Corbin, Kentucky, United States
Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Henry Ford Macomb Hospital - Clinton Township
🇺🇸Clinton Township, Michigan, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Spectrum Health Hospitals
🇺🇸Grand Rapids, Michigan, United States
McLaren Flint
🇺🇸Flint, Michigan, United States
Fairview Southdale
🇺🇸Edina, Minnesota, United States
ProMedica Monroe Regional Hospital
🇺🇸Monroe, Michigan, United States
Sanford Worthington Medical Center
🇺🇸Worthington, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Buffalo General Medical Center
🇺🇸Buffalo, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Mission Hospitals Inc
🇺🇸Asheville, North Carolina, United States
Guilford Neurologic Research
🇺🇸Greensboro, North Carolina, United States
Riverside Methodist Hospital; Cancer Services
🇺🇸Columbus, Ohio, United States
Doctors Hospital
🇺🇸Columbus, Ohio, United States
Ascension St. John
🇺🇸Tulsa, Oklahoma, United States
ProMedica Toledo Hospital
🇺🇸Toledo, Ohio, United States
UPMC East Hospital
🇺🇸Monroeville, Pennsylvania, United States
Uni of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Mercy
🇺🇸Pittsburgh, Pennsylvania, United States
UPMC Passavant Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Sanford Neurology Clinic
🇺🇸Sioux Falls, South Dakota, United States
Valley Baptist Medical Center-Brownsville
🇺🇸Brownsville, Texas, United States
Hamilton General Hospital; Pharmacy
🇨🇦Hamilton, Ontario, Canada
Valley Baptist Medical Center
🇺🇸Harlingen, Texas, United States
Ascension Seton Hays
🇺🇸Kyle, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Montreal Neurological Inst; Clinical Research Unit
🇨🇦Montreal, Quebec, Canada
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Dell Seton Medical center at the University of Texas
🇺🇸Austin, Texas, United States
University of Florida Health at Shands
🇺🇸Gainesville, Florida, United States
The Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Seton Medical Center Austin
🇺🇸Austin, Texas, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
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