A Study of the Efficacy and Safety of Alteplase in Participants With Mild Stroke

Stroke Clinical Trial

— PRISMS  

Official title:

A Phase IIIB, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02072226
• Other study ID #: ML29093
• Status: Terminated
• Phase: Phase 3
• Start date: May 31, 2014
• Est. completion date: March 22, 2017

Study information

• Verified date: June 2018
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PRISMS is a double-blind, multicenter, randomized, Phase IIIb study to evaluate the efficacy and safety of intravenous (IV) alteplase in participants with mild acute ischemic strokes that do not appear to be clearly disabling. Participants will be randomized in a 1:1 ratio to receive within 3 hours of last known well time either 1) one dose of IV alteplase and one dose of oral aspirin placebo or 2) one dose of IV alteplase placebo and one dose of oral aspirin 325 milligrams (mg).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 313
• Est. completion date: March 22, 2017
• Est. primary completion date: March 22, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Mild ischemic stroke defined as the most recent pre-treatment NIHSS score of less than or equal to(</=) 5 and determined as not clearly disabling by the investigator

• Study treatment initiated within 3 hours of last time participant seen normal

Exclusion Criteria:

• Computed tomography (CT) or magnetic resonance imaging (MRI) findings of one of the following:

1. CT with clear large hypodensity that is greater than (>) one-third middle cerebral artery (MCA) territory (or >100 cubic centimeter [cc] if not in MCA territory)

2. MRI with clear large hyperintensity on concurrent diffusion-weighted (DW) and fluid-attenuated inversion recovery (FLAIR) that is greater than one-third MCA territory (or greater than 100 cc if not in MCA territory),

3. Imaging lesion consistent with acute hemorrhage, or

4. Evidence of intraparenchymal tumor

• Disability prior to the presenting stroke

• Standard contraindications to IV alteplase within 3 hours of symptom onset, including:

1. Head trauma, myocardial infarction, or previous stroke within the previous 3 months

2. Gastrointestinal or urinary tract hemorrhage within the previous 21 days

3. Major surgery within the previous 14 days

4. Arterial puncture at non-compressible site within the previous 7 days

5. Any history of ICH with the exception of those less than (<) 5 chronic microbleeds on MRI

6. Elevated blood pressure defined by systolic blood pressure >185 millimeters of mercury (mm Hg) or diastolic blood pressure >110 mm Hg, or treatments requiring aggressive measures to achieve acceptable levels

7. Treatment with unfractioned heparin within past 48 hours and activated partial thromboplastin time outside normal range

8. Blood glucose <50 milligrams per deciliter (mg/dL)

9. International normalized ratio >1.7

10. Platelet count <100,000 per cubic millimeter (/mm^3)

11. Treatment with a direct thrombin inhibitor (dabigatran) or a factor Xa inhibitor (apixaban, rivaroxaban, edoxaban) within the last 48 hours

• Allergic reaction to study drug, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs)

• Females of childbearing age who are known to be pregnant and/or lactating

• Inability to swallow, which would prevent oral intake of aspirin or aspirin placebo tablet

• Other serious, advanced, or terminal illness that would confound the clinical outcome at 90 days

• Current or recent (within 3 months) participation in another investigational drug treatment protocol

• Anticipated inability to obtain 3-month follow-up assessments

• Previous enrollment in PRISMS

• Any other condition deemed by the investigator that would pose hazard to the participant with alteplase treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Alteplase
Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).
• Alteplase Placebo
Single dose of alteplase placebo will be administered as IV injection.
• Aspirin
Single dose of aspirin will be administered at 325 mg orally.
• Aspirin Placebo
Single dose of aspirin placebo will be administered orally.

Locations

Country	Name	City	State
United States	Akron General Medical Center	Akron	Ohio
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Nova Clinical Research, LLC	Bradenton	Florida
United States	Lutheran Medical Center	Brooklyn	New York
United States	SUNY Downstate Medical Center.	Brooklyn	New York
United States	Buffalo General Medical Center	Buffalo	New York
United States	University of North Carolina At Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina; MSC 300	Charleston	South Carolina
United States	Chattanooga Center for Neurologic Research	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Anderson Hospital	Cincinnati	Ohio
United States	Jewish Hospital	Cincinnati	Ohio
United States	The Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	West Hospital	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Missouri Health Care	Columbia	Missouri
United States	University of South Carolina School of Medicine	Columbia	South Carolina
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Associated Neurologists PC	Danbury	Connecticut
United States	Wright State University	Dayton	Ohio
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	St. Elizabeth Edgewood; Cancer Care Center" for Account St. Elizabeth Edgewood	Edgewood	Kentucky
United States	University of Louisville	Elizabethtown	Kentucky
United States	Alexian Brothers Neuroscience Institute	Elk Grove Village	Illinois
United States	Colorado Neurological Institute	Englewood	Colorado
United States	Inova Fairfax Hospital	Fairfax	Virginia
United States	Associated Neurologists of Southern CT PC	Fairfield	Connecticut
United States	Fairfield Hospital	Fairfield	Ohio
United States	St. Elizabeth Florence	Florence	Kentucky
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Neurologic Consultants, P.A.	Fort Lauderdale	Florida
United States	St. Elizabeth Fort Thomas	Fort Thomas	Kentucky
United States	Parkview Research Center	Fort Wayne	Indiana
United States	St. Jude Medical Center	Fullerton	California
United States	The Minneapolis Clinic of Neurology	Golden Valley	Minnesota
United States	Guilford Neurologic Associates	Greensboro	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Valley Baptist Medical Center	Harlingen	Texas
United States	Hartford Hospital	Hartford	Connecticut
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Methodist Neurological Institute	Houston	Texas
United States	University Of Texas Health Science Center Houston	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Gunderson Health System	La Crosse	Wisconsin
United States	University of California San Diego	La Jolla	California
United States	Sparrow Health System	Lansing	Michigan
United States	University of Kentucky	Lexington	Kentucky
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Medical Center of The Rockies	Loveland	Colorado
United States	Texas Tech Univ Health Sci Ctr	Lubbock	Texas
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Miami Miller School of Medicine; Clinical Reseach Building	Miami	Florida
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Columbia University Medical Center	New York	New York
United States	Ichan School of Medicine at Mount Sinai	New York	New York
United States	Christiana Care Health Services; Sponsor Programs Ammon Education Center	Newark	Delaware
United States	Hoag Memorial Hospital	Newport Beach	California
United States	The Neurology And Pain Clinic	Orangeburg	South Carolina
United States	Albert Einstein Healthcare Network	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	St Joesph Mercy Hospital Oakland	Pontiac	Michigan
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent's Medical Center	Portland	Oregon
United States	Northwest Hospital Center	Randallstown	Maryland
United States	Renown Health; Renown Institute for Neurosciences	Reno	Nevada
United States	Beaumont Hospital	Royal Oak	Michigan
United States	Washington University	Saint Louis	Missouri
United States	University Of Utah	Salt Lake City	Utah
United States	University Hospital San Antonio	San Antonio	Texas
United States	University of California Los Angeles	Santa Monica	California
United States	Swedish Medical Center	Seattle	Washington
United States	Overlook Hospital	Summit	New Jersey
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Shore Neurology	Toms River	New Jersey
United States	University of Arizona	Tucson	Arizona
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	York Hospital	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90	mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death prior to Day 90. Reported is the percentage of participants with scores of 0 or 1 on the mRS.	Day 90
Secondary	Distribution of Participants Across the Ordinal mRS	mRS score was determined by the investigator. The mRS is a 7 point scale (0-6) with 0: No symptoms at all, 1: No significant disability despite symptoms, able to carry out all usual duties and activities, 2: Slight disability, unable to carry out all previous activities but able to look after own affairs without assistance, 3: Moderate disability requiring some help, but able to walk without assistance, 4: Moderately severe disability, unable to walk without assistance and unable to attend to own bodily needs without assistance, 5: Severe disability, bedridden, incontinent and requiring constant nursing care and attention, 6: death before Day 90. Reported are the percentages of participants for all scores on the mRS.	Day 90
Secondary	Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS	Global favorable recovery is an integrated assessment of participants who meet the following: mRS Score 0-1, National Institutes of Health Stroke Scale (NIHSS) Score 0-1, Barthel Index [BI] greater than or equal to 95, and Glasgow Outcome Scale [GOS] equal to 1. mRS Score 0-1: 0= No symptoms at all, 1= No significant disability despite symptoms, able to carry out all usual duties and activities. NIHSS Score 0-1: 0= No stroke symptoms and 1= Minor stroke symptoms. BI is a 10 question index with a total score range of 0-100 with 100 being the best outcome. GOS =1: Good recovery. Reported here are the percentages of participants who achieved a favorable score on each of these scales.	Day 90
Secondary	Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH )	ICH was considered symptomatic if it was not seen on computed tomography (CT) or magnetic resonance imaging (MRI) scan at baseline and any neurologic decline was attributed to it by the local investigator. To detect intracranial hemorrhage, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.	Within 36 hours after study drug administration on Day 1
Secondary	Percentage of Participants With Any ICH	To detect ICH, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.	Within 36 hours after study drug administration on Day 1
Secondary	Overall Mortality	Reported here is the percentage of participants who died due to any cause during the study.	From baseline to Day 90
Secondary	Percentage of Participants Who Died Due to Stroke and Neurological Disorders	Reported here is the percentage of participants who died due to stroke and neurological disorders.	From baseline to Day 90
Secondary	Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	From baseline up to Day 90: Non-serious adverse events were collected through the Day 30 visit. Serious adverse events were collected through the end of study at Day 90.
Secondary	Percentage of Participants With Serious Adverse Events	A serious adverse event (SAE) was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.	From baseline to Day 90