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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02072226
• Collaborator: (none)
• Enrollment: 313
• Locations: 88
• Arms: 2
• Actual Duration (Months): 33.7
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Stroke	Drug: Alteplase; Drug: Alteplase Placebo; Drug: Aspirin; Drug: Aspirin Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 313 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 31, 2014
• Actual Primary Completion Date: Mar 22, 2017
• Actual Study Completion Date: Mar 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alteplase Placebo + Aspirin Participants will receive single dose of IV alteplase placebo and aspirin orally.	Drug: Alteplase Placebo; Single dose of alteplase placebo will be administered as IV injection.; Drug: Aspirin; Single dose of aspirin will be administered at 325 mg orally.
Experimental: Alteplase + Aspirin Placebo Participants will receive single dose of IV alteplase and aspirin placebo orally.	Drug: Alteplase; Single dose of alteplase will be administered at 0.9 milligrams per kilogram (mg/kg) IV (maximal dose of 90 mg).; Other Names: Activase; RO5532960 ; Drug: Aspirin Placebo; Single dose of aspirin placebo will be administered orally.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90 [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.

Secondary Outcome Measures

1. Distribution of Participants Across the Ordinal mRS [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 before Day 90. Reported are the percentages of participants for all scores on the mRS.

2. Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS [Day 90]

   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.

3. Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH ) [Within 36 hours after study drug administration on Day 1]

   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.

4. Percentage of Participants With Any ICH [Within 36 hours after study drug administration on Day 1]

   To detect ICH, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.

5. Overall Mortality [From baseline to Day 90]

   Reported here is the percentage of participants who died due to any cause during the study.

6. Percentage of Participants Who Died Due to Stroke and Neurological Disorders [From baseline to Day 90]

   Reported here is the percentage of participants who died due to stroke and neurological disorders.

7. Percentage of Participants With 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.]

   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.

8. Percentage of Participants With Serious Adverse Events [From baseline to Day 90]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
3	University of Arizona	Tucson	Arizona	United States	85724-5030
4	St. Jude Medical Center	Fullerton	California	United States	92835
5	University of California San Diego	La Jolla	California	United States	92093
6	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
7	Hoag Memorial Hospital	Newport Beach	California	United States	92658
8	University of California Los Angeles	Santa Monica	California	United States	90404
9	Colorado Neurological Institute	Englewood	Colorado	United States	80113
10	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
11	Medical Center of The Rockies	Loveland	Colorado	United States	80538
12	Associated Neurologists PC	Danbury	Connecticut	United States	06810
13	Associated Neurologists of Southern CT PC	Fairfield	Connecticut	United States	06824
14	Hartford Hospital	Hartford	Connecticut	United States	06102
15	Christiana Care Health Services; Sponsor Programs Ammon Education Center	Newark	Delaware	United States	19718-0002
16	Nova Clinical Research, LLC	Bradenton	Florida	United States	34209
17	Neurologic Consultants, P.A.	Fort Lauderdale	Florida	United States	33308
18	University of Miami Miller School of Medicine; Clinical Reseach Building	Miami	Florida	United States	33136
19	Northwestern University	Chicago	Illinois	United States	60611
20	Rush University Medical Center	Chicago	Illinois	United States	60612-3244
21	Alexian Brothers Neuroscience Institute	Elk Grove Village	Illinois	United States	60007
22	Parkview Research Center	Fort Wayne	Indiana	United States	46845
23	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
24	St. Elizabeth Edgewood; Cancer Care Center" for Account St. Elizabeth Edgewood	Edgewood	Kentucky	United States	41017
25	University of Louisville	Elizabethtown	Kentucky	United States	42791
26	St. Elizabeth Florence	Florence	Kentucky	United States	41042
27	St. Elizabeth Fort Thomas	Fort Thomas	Kentucky	United States	41075
28	University of Kentucky	Lexington	Kentucky	United States	40536
29	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
30	Northwest Hospital Center	Randallstown	Maryland	United States	21133
31	Detroit Receiving Hospital	Detroit	Michigan	United States	48201
32	Sparrow Health System	Lansing	Michigan	United States	48909
33	St Joesph Mercy Hospital Oakland	Pontiac	Michigan	United States	48341
34	Beaumont Hospital	Royal Oak	Michigan	United States	48073
35	The Minneapolis Clinic of Neurology	Golden Valley	Minnesota	United States	55422
36	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
37	University of Missouri Health Care	Columbia	Missouri	United States	65212
38	Washington University	Saint Louis	Missouri	United States	63128
39	Renown Health; Renown Institute for Neurosciences	Reno	Nevada	United States	89502
40	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
41	Overlook Hospital	Summit	New Jersey	United States	07902
42	Shore Neurology	Toms River	New Jersey	United States	08755
43	SUNY Downstate Medical Center.	Brooklyn	New York	United States	11203
44	Lutheran Medical Center	Brooklyn	New York	United States	11220
45	Buffalo General Medical Center	Buffalo	New York	United States	14203
46	Ichan School of Medicine at Mount Sinai	New York	New York	United States	10029
47	Columbia University Medical Center	New York	New York	United States	10032
48	University of North Carolina At Chapel Hill	Chapel Hill	North Carolina	United States	27514
49	Guilford Neurologic Associates	Greensboro	North Carolina	United States	27401
50	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
51	Akron General Medical Center	Akron	Ohio	United States	44307
52	University of Cincinnati	Cincinnati	Ohio	United States	45203-0542
53	West Hospital	Cincinnati	Ohio	United States	45211
54	The Christ Hospital	Cincinnati	Ohio	United States	45219
55	Jewish Hospital	Cincinnati	Ohio	United States	45236
56	Anderson Hospital	Cincinnati	Ohio	United States	45255
57	Case Western Reserve University	Cleveland	Ohio	United States	44109
58	Cleveland Clinic	Cleveland	Ohio	United States	44195
59	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
60	Wright State University	Dayton	Ohio	United States	45409
61	Fairfield Hospital	Fairfield	Ohio	United States	45014
62	University of Toledo Medical Center	Toledo	Ohio	United States	43614
63	Providence Portland Medical Center	Portland	Oregon	United States	97213
64	Providence Saint Vincent's Medical Center	Portland	Oregon	United States	97225
65	Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18105
66	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
67	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
68	Temple University Hospital	Philadelphia	Pennsylvania	United States	19140
69	Albert Einstein Healthcare Network	Philadelphia	Pennsylvania	United States	19141
70	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
71	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15219
72	York Hospital	York	Pennsylvania	United States	17403
73	Medical University of South Carolina; MSC 300	Charleston	South Carolina	United States	29425
74	University of South Carolina School of Medicine	Columbia	South Carolina	United States	29203-7606
75	The Neurology And Pain Clinic	Orangeburg	South Carolina	United States	29118
76	Chattanooga Center for Neurologic Research	Chattanooga	Tennessee	United States	37404
77	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
78	Valley Baptist Medical Center	Harlingen	Texas	United States	78550
79	Methodist Neurological Institute	Houston	Texas	United States	77030
80	University Of Texas Health Science Center Houston	Houston	Texas	United States	77030
81	Texas Tech Univ Health Sci Ctr	Lubbock	Texas	United States	79430
82	University Hospital San Antonio	San Antonio	Texas	United States	78229
83	University Of Utah	Salt Lake City	Utah	United States	84108
84	Inova Fairfax Hospital	Fairfax	Virginia	United States	22031
85	Swedish Medical Center	Seattle	Washington	United States	98122
86	West Virginia University Hospital	Morgantown	West Virginia	United States	26506
87	Gunderson Health System	La Crosse	Wisconsin	United States	54601
88	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Director: Clinical Trials, Genentech, Inc.

Study Documents (Full-Text)

• Statistical Analysis Plan - May 17, 2017
• Study Protocol - Jan 8, 2015

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT02072226
• Other Study ID Numbers: ML29093
• First Posted: Feb 26, 2014
• Last Update Posted: Jul 3, 2018
• Last Verified: Jun 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Stroke; Aspirin; Tissue Plasminogen Activator

Study Results

Participant Flow

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 milligram per kilogram (mg/kg) (maximal dose of 90 mg) intravenous (IV) alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Period Title: Overall Study
STARTED	156	157
COMPLETED	141	147
NOT COMPLETED	15	10

Baseline Characteristics

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin	Total
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.	Total of all reporting groups
Overall Participants	156	157	313
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.94 (13.53)	61.20 (13.05)	61.57 (13.27)
Sex: Female, Male (Count of Participants)
Female	79 50.6%	65 41.4%	144 46%
Male	77 49.4%	92 58.6%	169 54%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	14 9%	18 11.5%	32 10.2%
Not Hispanic or Latino	138 88.5%	135 86%	273 87.2%
Not Reported	4 2.6%	3 1.9%	7 2.2%
Unknown	0 0%	1 0.6%	1 0.3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.6%	3 1.9%	4 1.3%
Asian	0 0%	1 0.6%	1 0.3%
Black or African American	35 22.4%	27 17.2%	62 19.8%
White	117 75%	126 80.3%	243 77.6%
Other	1 0.6%	0 0%	1 0.3%
Unknown	2 1.3%	0 0%	2 0.6%
Total National Institutes of Health Stroke Scale (NIHSS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.3 (1.21)	2.1 (1.15)	2.2 (1.18)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Modified Rankin Scale (mRS) Score of 0 or 1 at Day 90
Description	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.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population included all randomized participants.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	156	157
Number [percentage of participants]	78.2 50.1%	81.5 51.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alteplase + Aspirin Placebo, Alteplase Placebo + Aspirin
	Comments
	Type of Statistical Test	Other
	Comments	Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Risk Difference
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95%; -9.44 to 7.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Distribution of Participants Across the Ordinal mRS
Description	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.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	156	157
mRS at Day 90 - 0	44.9 28.8%	50.3 32%
mRS at Day 90 - 1	33.3 21.3%	31.2 19.9%
mRS at Day 90 - 2	11.5 7.4%	11.5 7.3%
mRS at Day 90 - 3	2.6 1.7%	3.2 2%
mRS at Day 90 - 4	5.1 3.3%	2.5 1.6%
mRS at Day 90 - 5 or 6 (death)	2.6 1.7%	1.3 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alteplase + Aspirin Placebo, Alteplase Placebo + Aspirin
	Comments
	Type of Statistical Test	Other
	Comments	Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.810
	Confidence Interval	(2-Sided) 95%; 0.527 to 1.244
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Global Favorable Recovery on mRS, NIHSS, BI, and GOS
Description	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.
Time Frame	Day 90

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	156	157
mRS 0 - 1 at Day 90	78.2 50.1%	81.5 51.9%
NIHSS 0 - 1 at Day 90	85.0 54.5%	81.7 52%
BI >= 95 at Day 90	79.3 50.8%	88.7 56.5%
GOS = 1 at Day 90	81.5 52.2%	85.6 54.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alteplase + Aspirin Placebo, Alteplase Placebo + Aspirin
	Comments
	Type of Statistical Test	Other
	Comments	Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.858
	Confidence Interval	(2-Sided) 95%; 0.529 to 1.393
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Symptomatic Intracranial Hemorrhage (ICH )
Description	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.
Time Frame	Within 36 hours after study drug administration on Day 1

Outcome Measure Data

Analysis Population Description

Safety Population included all participants, who received any amount of study drug.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	154	153
Number [percentage of participants]	3.2 2.1%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alteplase + Aspirin Placebo, Alteplase Placebo + Aspirin
	Comments
	Type of Statistical Test	Other
	Comments	Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	3.25
	Confidence Interval	(2-Sided) 95%; 0.75 to 7.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants With Any ICH
Description	To detect ICH, neuroimaging (CT or MRI) scan was performed at 22 to 36 hours after study drug administration.
Time Frame	Within 36 hours after study drug administration on Day 1

Outcome Measure Data

Analysis Population Description

Safety Population included all participants, who received any amount of study drug.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	154	153
Any ICH within 36 hours reported by site	7.1 4.6%	2.6 1.7%
Any ICH within 36 hours reported by central reader	7.1 4.6%	3.3 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alteplase + Aspirin Placebo, Alteplase Placebo + Aspirin
	Comments	Any ICH within 36 hours reported by site
	Type of Statistical Test	Other
	Comments	Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	4.53
	Confidence Interval	(2-Sided) 95%; -0.34 to 10.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alteplase + Aspirin Placebo, Alteplase Placebo + Aspirin
	Comments	Any ICH within 36 hours reported by central reader
	Type of Statistical Test	Other
	Comments	Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	difference in percentages
	Estimated Value	3.87
	Confidence Interval	(2-Sided) 95%; -1.23 to 9.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Overall Mortality
Description	Reported here is the percentage of participants who died due to any cause during the study.
Time Frame	From baseline to Day 90

Outcome Measure Data

Analysis Population Description

Safety Population included all participants, who received any amount of study drug.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	154	153
Number [percentage of participants]	0.6 0.4%	0 0%

7. Secondary Outcome

Title	Percentage of Participants Who Died Due to Stroke and Neurological Disorders
Description	Reported here is the percentage of participants who died due to stroke and neurological disorders.
Time Frame	From baseline to Day 90

Outcome Measure Data

Analysis Population Description

Safety Population included all participants, who received any amount of study drug.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	154	153
Number [percentage of participants]	0 0%	0 0%

8. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety Population included all participants, who received any amount of study drug.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	154	153
Number [percentage of participants]	77.3 49.6%	68.0 43.3%

9. Secondary Outcome

Title	Percentage of Participants With Serious Adverse Events
Description	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.
Time Frame	From baseline to Day 90

Outcome Measure Data

Analysis Population Description

Safety Population included all participants, who received any amount of study drug.

Arm/Group Title	Alteplase + Aspirin Placebo	Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.	Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
Measure Participants	154	153
Number [percentage of participants]	26.0 16.7%	13.1 8.3%

Adverse Events

Time Frame	Serious adverse events were collected from baseline through the end of study at Day 90. Non-serious adverse events were collected from baseline through the Day 30 visit.
Adverse Event Reporting Description	Safety population included all participants, who received any amount of study drug.
Arm/Group Title	Alteplase + Aspirin Placebo		Alteplase Placebo + Aspirin
Arm/Group Description	Participants received single dose of 0.9 mg/kg (maximal dose of 90 mg) IV alteplase and aspirin placebo orally.		Participants received single dose of IV alteplase placebo and 325 mg aspirin orally.
All Cause Mortality
	Alteplase + Aspirin Placebo		Alteplase Placebo + Aspirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/154 (0.6%)		0/153 (0%)
Serious Adverse Events
	Alteplase + Aspirin Placebo		Alteplase Placebo + Aspirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/154 (26%)		20/153 (13.1%)
Blood and lymphatic system disorders
Anaemia	1/154 (0.6%)		0/153 (0%)
Splenic embolism	0/154 (0%)		1/153 (0.7%)
Cardiac disorders
Cardiac failure	2/154 (1.3%)		0/153 (0%)
Cardiogenic shock	2/154 (1.3%)		0/153 (0%)
Sinus node dysfunction	1/154 (0.6%)		1/153 (0.7%)
Acute left ventricular failure	1/154 (0.6%)		0/153 (0%)
Acute myocardial infarction	0/154 (0%)		1/153 (0.7%)
Cardiac aneurysm	0/154 (0%)		1/153 (0.7%)
Cardiac failure acute	1/154 (0.6%)		0/153 (0%)
Cardiac failure congestive	1/154 (0.6%)		0/153 (0%)
Cardiomyopathy	1/154 (0.6%)		0/153 (0%)
Ear and labyrinth disorders
Vertigo	0/154 (0%)		1/153 (0.7%)
Vertigo positional	1/154 (0.6%)		0/153 (0%)
Eye disorders
Retinal detachment	0/154 (0%)		1/153 (0.7%)
Vitreous haemorrhage	1/154 (0.6%)		0/153 (0%)
Gastrointestinal disorders
Diarrhoea	0/154 (0%)		1/153 (0.7%)
Duodenal ulcer	1/154 (0.6%)		0/153 (0%)
Gastritis	0/154 (0%)		1/153 (0.7%)
Nausea	1/154 (0.6%)		0/153 (0%)
Volvulus	1/154 (0.6%)		0/153 (0%)
General disorders
Asthenia	0/154 (0%)		1/153 (0.7%)
Gait disturbance	1/154 (0.6%)		0/153 (0%)
Immune system disorders
Anaphylactic reaction	1/154 (0.6%)		0/153 (0%)
Infections and infestations
Urinary tract infection	2/154 (1.3%)		0/153 (0%)
Ophthalmic herpes zoster	1/154 (0.6%)		0/153 (0%)
Pneumonia	1/154 (0.6%)		0/153 (0%)
Injury, poisoning and procedural complications
Fall	0/154 (0%)		1/153 (0.7%)
Fracture displacement	1/154 (0.6%)		0/153 (0%)
Subarachnoid haemorrhage	0/154 (0%)		1/153 (0.7%)
Investigations
Haemoglobin decreased	1/154 (0.6%)		0/153 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/154 (0.6%)		0/153 (0%)
Hyperkalaemia	1/154 (0.6%)		0/153 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	1/154 (0.6%)		0/153 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign ovarian tumour	1/154 (0.6%)		0/153 (0%)
Bladder cancer	1/154 (0.6%)		0/153 (0%)
Lung neoplasm malignant	1/154 (0.6%)		0/153 (0%)
Nervous system disorders
Ischaemic stroke	5/154 (3.2%)		2/153 (1.3%)
Stroke in evolution	5/154 (3.2%)		1/153 (0.7%)
Seizure	2/154 (1.3%)		2/153 (1.3%)
Transient ischaemic attack	1/154 (0.6%)		3/153 (2%)
Haemorrhagic transformation stroke	2/154 (1.3%)		1/153 (0.7%)
Carotid artery stenosis	1/154 (0.6%)		1/153 (0.7%)
Cerebral haemorrhage	2/154 (1.3%)		0/153 (0%)
Cerebrovascular accident	0/154 (0%)		2/153 (1.3%)
Haemorrhage intracranial	2/154 (1.3%)		0/153 (0%)
Carotid arteriosclerosis	0/154 (0%)		1/153 (0.7%)
Embolic stroke	0/154 (0%)		1/153 (0.7%)
Hemiparesis	1/154 (0.6%)		0/153 (0%)
Ischaemic cerebral infarction	1/154 (0.6%)		0/153 (0%)
Sciatica	1/154 (0.6%)		0/153 (0%)
Toxic encephalopathy	1/154 (0.6%)		0/153 (0%)
Tremor	0/154 (0%)		1/153 (0.7%)
Product Issues
Device loosening	1/154 (0.6%)		0/153 (0%)
Renal and urinary disorders
Acute kidney injury	1/154 (0.6%)		0/153 (0%)
Renal embolism	0/154 (0%)		1/153 (0.7%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/154 (0%)		1/153 (0.7%)
Respiratory distress	1/154 (0.6%)		0/153 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/154 (0.6%)		1/153 (0.7%)
Vascular disorders
Deep vein thrombosis	1/154 (0.6%)		0/153 (0%)
Hypotension	0/154 (0%)		1/153 (0.7%)
Orthostatic hypotension	1/154 (0.6%)		0/153 (0%)
Other (Not Including Serious) Adverse Events
	Alteplase + Aspirin Placebo		Alteplase Placebo + Aspirin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/154 (31.8%)		53/153 (34.6%)
Gastrointestinal disorders
Nausea	9/154 (5.8%)		13/153 (8.5%)
Constipation	8/154 (5.2%)		10/153 (6.5%)
Metabolism and nutrition disorders
Hyperlipidaemia	7/154 (4.5%)		12/153 (7.8%)
Hypokalaemia	9/154 (5.8%)		9/153 (5.9%)
Nervous system disorders
Headache	25/154 (16.2%)		26/153 (17%)
Vascular disorders
Hypertension	11/154 (7.1%)		10/153 (6.5%)

Limitations/Caveats

The study was terminated early due to low enrollment, leading to smaller number of participants analyzed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.