Trial Outcomes & Findings for Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation (NCT NCT02283294)

NCT ID: NCT02283294

Last Updated: 2021-11-30

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

180 days

Results posted on

2021-11-30

Participant Flow

Ninety one patients were enrolled/consented into the study. Three patients of the 91 consented did not meet one or more of the inclusion/exclusion criteria and were excluded prior to randomization assignment.

Participant milestones

Participant milestones
Measure	Apixaban Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin
Overall Study STARTED	41	47
Overall Study Received Allocated Treatment Intervention	38	31
Overall Study COMPLETED	38	39
Overall Study NOT COMPLETED	3	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	1	6
Overall Study Protocol Violation	1	0
Overall Study Thrombus on transesophageal echocardiogram	0	1

Baseline Characteristics

Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban n=41 Participants Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin n=47 Participants standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin	Total n=88 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	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical >=65 years	28 Participants n=5 Participants	35 Participants n=7 Participants	63 Participants n=5 Participants
Age, Continuous	72.6 years STANDARD_DEVIATION 14.9 • n=5 Participants	74.3 years STANDARD_DEVIATION 10.5 • n=7 Participants	73.5 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	24 Participants n=7 Participants	39 Participants n=5 Participants
Race/Ethnicity, Customized Black	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic White	31 Participants n=5 Participants	35 Participants n=7 Participants	66 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants	47 participants n=7 Participants	88 participants n=5 Participants
Hypertension	38 Participants n=5 Participants	46 Participants n=7 Participants	84 Participants n=5 Participants
Hyperlipidemia	24 Participants n=5 Participants	34 Participants n=7 Participants	58 Participants n=5 Participants
Coronary artery disease (CAD)	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Diabetes Mellitus	10 Participants n=5 Participants	22 Participants n=7 Participants	32 Participants n=5 Participants
Peripheral Artery Disease	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Prior Stroke	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Prosthetic Heart Valve / Valve Replacement	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Thyroid Disease	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Obstructive Sleep Apnea	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Congestive Heart Failure Symptoms	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Past Medical History Left Ventricular Ejection Fraction < 40%	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Chronic Kidney Disease Stage 3	7 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants
Chronic Kidney Disease Stage 4	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Chronic Kidney Disease Stage 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Transient Ischemic Attack	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Thromboembolism History	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
New Onset Atrial Fibrillation	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Prior Use of Anticoagulation within last 3 months	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Former Tobacco Use History	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Former Alcohol Use History	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Former Illegal Drug Use History	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Height	1.67 m STANDARD_DEVIATION 0.11 • n=5 Participants	1.712 m STANDARD_DEVIATION 0.14 • n=7 Participants	1.69 m STANDARD_DEVIATION 0.13 • n=5 Participants
Weight	82.10 kg STANDARD_DEVIATION 24.09 • n=5 Participants	88.08 kg STANDARD_DEVIATION 24.73 • n=7 Participants	85.29 kg STANDARD_DEVIATION 24.48 • n=5 Participants
Body Mass Index	29.15 kg/m^2 STANDARD_DEVIATION 6.68 • n=5 Participants	30.05 kg/m^2 STANDARD_DEVIATION 7.60 • n=7 Participants	29.63 kg/m^2 STANDARD_DEVIATION 7.16 • n=5 Participants
Body Surface Area	1.90 m^2 STANDARD_DEVIATION 0.28 • n=5 Participants	1.99 m^2 STANDARD_DEVIATION 0.31 • n=7 Participants	1.95 m^2 STANDARD_DEVIATION 0.30 • n=5 Participants
Heart Rate	76.56 bpm STANDARD_DEVIATION 14.46 • n=5 Participants	76.62 bpm STANDARD_DEVIATION 16.61 • n=7 Participants	76.60 bpm STANDARD_DEVIATION 15.56 • n=5 Participants
Systolic Blood Pressure	130.85 mmHg STANDARD_DEVIATION 18.64 • n=5 Participants	134.53 mmHg STANDARD_DEVIATION 20.13 • n=7 Participants	132.82 mmHg STANDARD_DEVIATION 19.43 • n=5 Participants
Current Tobacco Use	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Occasional Tobacco Use	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Current Alcohol Use	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Occasional Alcohol Use	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Diastolic Blood Pressure	74.07 mmHg STANDARD_DEVIATION 17.76 • n=5 Participants	70.26 mmHg STANDARD_DEVIATION 19.50 • n=7 Participants	72.03 mmHg STANDARD_DEVIATION 18.70 • n=5 Participants

PRIMARY outcome

Timeframe: 180 days

Outcome measures

Outcome measures
Measure	Apixaban n=41 Participants Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin n=47 Participants Standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin
Number of Participants With a Composite Endpoint of Fatal Stroke, Recurrent Ischemic Stroke, or TIA	7 Participants	12 Participants

SECONDARY outcome

Timeframe: 180 days

Outcome measures

Outcome measures
Measure	Apixaban n=41 Participants Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin n=47 Participants Standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin
Number of Participants With an Intracranial Hemorrhage Assessed by MRI/CT	5 Participants	6 Participants

Adverse Events

Apixaban

Serious events: 11 serious events

Other events: 36 other events

Deaths: 2 deaths

Warfarin

Serious events: 14 serious events

Other events: 41 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

David Rose, MD

University of South Florida

Phone: 813-259-8577

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Apixaban n=41 participants at risk Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin n=47 participants at risk standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin
Endocrine disorders Pancreatic Cancer	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Third Degree AV Block	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Fatal Stroke	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	6.4% 3/47 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Worsening Congestive Heart Failure	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Left Hip Fracture	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Worsening Atrial Fibrillation	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Symptomatic Hypotension	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Symptomatic PH1 Hemorrhagic Transformation	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders TIA	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders GI Bleed	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders Small Bowel Obstruction	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders Pancolitis	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Acute Encephalopathy	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Reproductive system and breast disorders Ovarian Cyst	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Second Digit Right Foot Amputation	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Recurrent Stroke	12.2% 5/41 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	14.9% 7/47 • Number of events 7 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Back Fracture	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Worsening Back Pain	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Bilateral Leg Weakness / Trouble with Ambulation	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Right Hip Pain	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Altered Mental Status	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Metabolic Encephalopathy	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Shortness of Breath	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Blood and lymphatic system disorders Symptomatic Anemia	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Ostectomy Left Foot	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.

Other adverse events
Measure	Apixaban n=41 participants at risk Apixaban twice a day for 180 days with drug initiation day 0-3 (TIA), day 3-5(small stroke) or day 7- 9 (medium stroke) respectively Apixaban	Warfarin n=47 participants at risk standard of care warfarin starting at day 7±5 (TIA) or day 14 ±5 (small to medium ischemic stroke). Warfarin
Cardiac disorders Fatigue	12.2% 5/41 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	10.6% 5/47 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Dizziness	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	19.1% 9/47 • Number of events 10 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Shortness of Breath	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	8.5% 4/47 • Number of events 4 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders Vomiting	7.3% 3/41 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	10.6% 5/47 • Number of events 6 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Sinus Bradycardia	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Back Pain	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	6.4% 3/47 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Intermittent Headaches	12.2% 5/41 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	10.6% 5/47 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Renal and urinary disorders Urinary Tract Infection	14.6% 6/41 • Number of events 6 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	6.4% 3/47 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Asymptomatic Bleed	12.2% 5/41 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	10.6% 5/47 • Number of events 5 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Fever	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Difficulty Finding Words	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Intermittent Cognitive Impairment	7.3% 3/41 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Renal and urinary disorders Acute Kidney Injury	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Bilateral Lower Extremity Edema	24.4% 10/41 • Number of events 11 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	6.4% 3/47 • Number of events 4 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Intermittent Leg Cramping	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Body / Muscle Aches	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	6.4% 3/47 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Back Pain with Ambulation	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Right Hip Pain	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Cough	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Dry Mouth	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Altered Sense of Taste	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Left Calf Sore	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Hypertension	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Lower Back Pain	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Palpitations	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Cold Symptoms	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Sore Throat	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Worsening Hearing Loss	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Musculoskeletal and connective tissue disorders Gout Right Foot	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	0.00% 0/47 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders Diarrhea	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	4.3% 2/47 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Ataxia	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders Constipation	2.4% 1/41 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Right or Left Sided Weakness	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Shakiness	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Intermittent Lightheadedness	4.9% 2/41 • Number of events 2 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Blood Clot in Descending Aorta	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
General disorders Bronchitis	7.3% 3/41 • Number of events 3 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Cardiac disorders Pleuritic Chest Pain	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.
Gastrointestinal disorders Decreased Appetite	0.00% 0/41 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.	2.1% 1/47 • Number of events 1 • 210 +/- 10 days Adverse event assessment was performed at each of the patient follow up visits at baseline, day 14, day 30, day 60, day 120, day 150, day 180, and day 210. At each follow up visit, patients were evaluated by study coordinator, cardiologist, and neurologist. A physical exam, patient interview, electrocardiogram, and review of patient records were performed. Labs were evaluated for clinical significance at day 30, day 90, and day 180 visits.