Trial Outcomes & Findings for Combination Anti-Platelet and Anti-Coagulation Treatment After Lysis of Ischemic Stroke Trial (CATALIST) (NCT NCT00061373)

Last Updated: 2013-02-04

Results Overview

This is a primary safety outcome or toxicity measure for all subjects. Symptomatic ICH is defined as the presence of two conditions: evidence of hemorrhage on the 72-hour head CT and an increase in the NIHSS score of 4 or more points from the prior examination. Hemorrhage classifications are according to European Cooperative Acute Stroke Study (ECASS). The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extra ocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patient's ability to answer questions and perform activities. Ratings for each of the 15 items are scored. Patients who have a score of 0 are considered to have "normal" examination. Patients with a score of 40 have the most severe stroke symptoms.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

From the start of study drugs and prior to the 72-hour safety head CT

Results posted on

2013-02-04

Participant Flow

Recruitment for this clinical trial opened in 2004 and closed in 2009. Patients who presented to one of two metropolitan Washington, DC hospitals with acute ischemic stroke and who treated with standard iv tPA were screened for study enrollment.

Enrollment into the MRI was preferential. If patients had contraindications to MRI or acquisition of MRI delayed treatment with iv tPA, they were enrolled in the non-MRI arm of the study.

Participant milestones

Participant milestones
Measure	MRI- Selected Patients Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Overall Study STARTED	15	3
Overall Study Aspirin and Tinzaparin	15	3
Overall Study COMPLETED	15	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Anti-Platelet and Anti-Coagulation Treatment After Lysis of Ischemic Stroke Trial (CATALIST)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MRI- Selected Patients n=15 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 Participants Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	1 Participants n=7 Participants	11 Participants n=5 Participants
Age Continuous	70 years STANDARD_DEVIATION 9 • n=5 Participants	59 years STANDARD_DEVIATION 7 • n=7 Participants	68 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	3 participants n=7 Participants	18 participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of study drugs and prior to the 72-hour safety head CT

Population: All patients had a 72-hour safety head CT performed

Outcome measures

Outcome measures
Measure	MRI- Selected Patients n=15 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 Participants Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Symptomatic Intracerebral Hemorrhage (ICH)	1 participants	1 participants

PRIMARY outcome

Timeframe: From the start of study drugs and prior to 72-hour head CT

Population: All patients completed 72-hour safety evaluation

Major systemic hemorrhage is defined bleeding associated with an adjusted decrease in hemoglobin of greater than 5 grams per diluent (g/dL), or and adjusted decrease in hematocrit greater than or equal to 15 percentage points or bleeding causing persistent or significant disability or incapacity such as hemorrhage in the eye.

Outcome measures

Outcome measures
Measure	MRI- Selected Patients n=15 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 Participants Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Major Systemic Hemorrhage	0 participants	0 participants

PRIMARY outcome

Timeframe: From start of study drugs and prior to 72-hour head CT

Population: All Patients completed 72-hour study safety evaluation

This is a primary safety outcome for all subjects.

Outcome measures

Outcome measures
Measure	MRI- Selected Patients n=15 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 Participants Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Other Serious Adverse Event Related to Study Drug Administration, Including Death.	0 participants	0 participants

PRIMARY outcome

Timeframe: up to 24 hours from the start of study drugs

Population: Complete reperfusion at 2 and 24 hours was measured in MRI-selected patients only.

This is the primary response outcome measure for patients in the MRI arm. A positive response is measured by evidence of complete reperfusion (or restoration of blood flow)on the perfusion weighted images (PWI) and mean transit time (MTT) maps of MRIs at 2 hours and sustained at 24 hours.

Outcome measures

Outcome measures
Measure	MRI- Selected Patients n=14 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
MRI Selected Arm: Complete Brain Reperfusion	0 participants	—

PRIMARY outcome

Timeframe: up to 24 hours from the start of study drugs

Population: Clinical improvement on NIHSS of 7 points or greater at 72 hours is the primary response outcome for non-MRI selected patients. Clinical response outcome was analyzed on all patients enrolled; MRI selected and non-selected patients.

This is the primary response outcome measure for subjects in the non-MRI arm. A positive response is measured by a 7 point or more improvement in the NIHSS or for those with less than 7 points at baseline,complete resolution of stroke symptoms. The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute stroke on the levels of consciousness, language, neglect, visual-field loss, extra ocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patient's ability to answer questions and perform activities. Ratings for each of the 15 items are scored. Patients who have a score of 0 are considered to have "normal" examination. Patients with a score of 40 have the most severe stroke symptoms.

Outcome measures

Outcome measures
Measure	MRI- Selected Patients n=15 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 Participants Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Non-MRI Selected Arm: Substantial Clinical Recovery (Non-MRI Arm)	3 participants	2 participants

SECONDARY outcome

Timeframe: 2 hr, 24 hr, 72 hr, 5 days, 30 days from start of study drugs

Population: All bleeding events that occurred among all patients enrolled and throughout the 30-day trial period but not classified as a primary outcome event. Bleeding events in this category include asymptomatic ICH(aICH);major systemic bleeding after 72 hours or minor and non-significant bleeding at anytime within the 30-day period.

Bleeding events of any type, severity and at any time throughout the 30-day trial period.

Outcome measures

Outcome measures
Measure	MRI- Selected Patients n=15 Participants Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 Participants Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Bleeding Events	8 participants	1 participants

Adverse Events

MRI- Selected Patients

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Non-MRI Selected Patients

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MRI- Selected Patients n=15 participants at risk Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 participants at risk Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Nervous system disorders Neurological Worsening	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Symptomatic ICH	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Vascular disorders Deep Vein Thrombosis	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	66.7% 2/3 • Number of events 2 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Cardiac disorders Non-ST Segment Elevation Myocardial Infarction (NSTEMI)	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Blood and lymphatic system disorders Systemic Bleeding/Anemia	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Endocrine disorders Metabolic Disturbance	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Renal and urinary disorders Urinary Tract Infection	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.

Other adverse events

Additional Information

Steven Warach, MD, PhD; Principal Investigator

NIH/NINDS and University of Texas Southwestern, Clinical Research Institute of Austin

Phone: 512-324-8383

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	MRI- Selected Patients n=15 participants at risk Patients eligible for the MRI arm met all clinical and MRI inclusion and exclusion criteria. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.	Non-MRI Selected Patients n=3 participants at risk Patients eligible for the non-MRI arm met all clinical inclusion-exclusion criteria, had MRI is contraindications or the acquisition of MRI would have compromised iv tPA delivery within the standard treatment window. Patients received a single dose of aspirin 81 mg orally (or rectal dose equivalent)and a single SQ dose of tinzaparin sodium, 80 anti-Xa IU/kg as soon after iv tPA and consent but within 6 hours of the start of iv tPA.
Infections and infestations Fever	26.7% 4/15 • Number of events 5 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Headache	33.3% 5/15 • Number of events 5 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	66.7% 2/3 • Number of events 2 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Respiratory, thoracic and mediastinal disorders Metabolic Alkalosis	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Metabolism and nutrition disorders Electrolyte imbalance	13.3% 2/15 • Number of events 4 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Musculoskeletal and connective tissue disorders Pain, lower extremity	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Cardiac disorders Sinus bradycardia, asymptomatic	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Cardiac disorders Atrial Fibrillation	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Cardiac disorders Hypotension	13.3% 2/15 • Number of events 3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Cardiac disorders Sick Sinus Syndrome	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Asymptomatic ICH	40.0% 6/15 • Number of events 6 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Ischemic Stroke, New	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Expansion of ischemic stroke	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Skin and subcutaneous tissue disorders Cellulitis	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Hepatobiliary disorders Elevated Liver Enzymes	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Gastrointestinal disorders Nausea	0.00% 0/15 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Gastrointestinal disorders Vomiting	13.3% 2/15 • Number of events 2 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Renal and urinary disorders Urinary Tract Infection	13.3% 2/15 • Number of events 2 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	33.3% 1/3 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Renal and urinary disorders Hematuria	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Agitation	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Mood Alteration	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Nervous system disorders Neurological Worsening	13.3% 2/15 • Number of events 2 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Respiratory, thoracic and mediastinal disorders Labored Breathing	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.
Respiratory, thoracic and mediastinal disorders Pulmonary Congestion	6.7% 1/15 • Number of events 1 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.	0.00% 0/3 • Adverse events were monitored from the start of study drug administration through the 30-day study period. All cases of ICH were reported to and reviewed by the DSMB. Patients with symptomatic ICH prior to the 72-hour head CT were reviewed by the DSMB prior to enrollment of new patients.