Sustained Treatment of Paroxysmal Atrial Fibrillation Post-Approval Study (STOP AF PAS)

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01456949
• Collaborator: (none)
• Enrollment: 402
• Locations: 39
• Arm: 1
• Actual Duration (Months): 65.1
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The Post-Approval Study (PAS) is a prospective multi-center, non-randomized, single arm, controlled,unblinded clinical study designed to provide long-term safety and effectiveness of the Arctic Front® Cardiac CryoAblation System.

Condition or Disease	Intervention/Treatment	Phase
Paroxysmal Atrial Fibrillation (PAF)	Device: Medtronic Arctic Front® Cardiac CryoAblation System	N/A

Detailed Description

Safety and effectiveness will be evaluated against pre-specified performance criteria as determined by the sponsor and FDA. The criteria set in this study have been previously used to demonstrate safety and effectiveness in cryoablation and radio-frequency ablation for the treatment of paroxysmal atrial fibrillation.

The analyses of the primary effectiveness objective will take place once all the subjects with a study cryoablation procedure attempt have reached 36 months of follow-up post-cryoablation procedure. The analysis of the primary safety objective will take place once all the subjects with a study cryoablation procedure attempt have reached 12 months of follow-up post-cryoablation procedure. The analyses for the secondary objectives will take place once all subjects with a study cryoablation attempt have reached 36 months of follow-up post-cryoablation procedure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 402 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sustained Treatment of Paroxysmal Atrial Fibrillation Post-Approval Study (STOP AF PAS)
• Actual Study Start Date: Jun 26, 2012
• Actual Primary Completion Date: Nov 30, 2017
• Actual Study Completion Date: Nov 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Single Arm Cryoablation	Device: Medtronic Arctic Front® Cardiac CryoAblation System; Cardiac cryoablation to isolate the pulmonary veins using the Arctic Front® CryoAblation System, with point ablation using the Freezor® Max as needed.; Other Names: Medtronic CryoCath CryoConsole Arctic Front® Cardiac CryoAblation Catheter Arctic Front Advance™ Cardiac CryoAblation Catheter Freezor® MAX Cardiac CryoAblation Catheter

Outcome Measures

Primary Outcome Measures

1. Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) Through 36 Months [Through 36 months]

   Evaluated by assessing the rate of subjects free of chronic treatment failure with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs). Chronic treatment failure is defined as: Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period)

2. Safety: Percentage of Participants Experiencing Cryoablation Procedure Events (CPEs) Through 12 Months [12 Months]

   Demonstrate safety (through 12 months) of Arctic Front® Cardiac CryoAblation Catheter System, including the Freezor® MAX Cardiac Cryoablation Catheter by assessing the rate of subjects experiencing Cryoablation Procedure Events (CPEs) with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs).

Secondary Outcome Measures

1. Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years. [Annually, through 3 years]

   Freedom from Major Atrial Fibrillation Event (MAFE): A MAFE is a serious adverse event (SAE) which has not been categorized as a cryoablation procedure event.

2. Chronic Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) at 1 and 2 Years [Annually, at 1 and 2 years]

   Freedom from chronic treatment failure, defined as: Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Documented PAF:

• Diagnosis of paroxysmal atrial fibrillation (PAF), AND

• 2 or more episodes of AF during the 3 months preceding the consent Date, AND

• At least 1 episode of AF documented with a tracing within 12 months preceding the consent date.

1. Age 18 years or older

2. Failure for the treatment of AF (effectiveness or intolerance) of at least one membrane active AAD for rhythm control.

Exclusion Criteria:

1. Any previous left atrial (LA) ablation (except permissible retreatment subjects)

2. Any previous LA surgery

3. Current intracardiac thrombus (can be treated after thrombus is resolved)

4. Presence of any pulmonary vein stents

5. Presence of any pre-existing pulmonary vein stenosis

6. Pre-existing hemidiaphragmatic paralysis

7. Anteroposterior LA diameter > 5.5 cm by TTE

8. Presence of any cardiac valve prosthesis

9. Clinically significant mitral valve regurgitation or stenosis

10. Myocardial infarction, PCI / PTCA or coronary artery stenting which occurred during the 3 month interval preceding the Consent Date

11. Unstable angina

12. Any cardiac surgery which occurred during the 3 month interval preceding the Consent Date

13. Any significant congenital heart defect corrected or not (including atrial septal defects or pulmonary vein abnormalities but not including minor PFO)

14. NYHA class III or IV congestive heart failure

15. Left ventricular ejection fraction (LVEF) < 40%

16. 2º (Type II) or 3º atrioventricular block

17. Presence of a permanent pacemaker, biventricular pacemaker, atrial defibrillator or any type of implantable cardiac defibrillator (with or without biventricular pacing function)

18. Brugada syndrome

19. Long QT syndrome

20. Arrhythmogenic right ventricular dysplasia

21. Sarcoidosis

22. Hypertrophic cardiomyopathy

23. Known cryoglobulinemia

24. Uncontrolled hyperthyroidism

25. Any cerebral ischemic event (strokes or TIAs) which occurred during the 6 month interval preceding the Consent Date.

26. Any woman known to be pregnant

27. Life expectancy less than one (1) year

28. Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of this study not pre-approved by Medtronic

29. Unwilling or unable to comply fully with study procedures and followup

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Heart Institute	Anchorage	Alaska	United States	99508
2	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
3	Good Samaritan Hospital	San Jose	California	United States	95124
4	Colorado Heart and Vascular	Denver	Colorado	United States	80204
5	Daytona Heart Group	Daytona Beach	Florida	United States	32114
6	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
7	University of Florida	Gainesville	Florida	United States	32610
8	Emory University Hospital	Atlanta	Georgia	United States	30322
9	WellStar Kennestone Hospital	Marietta	Georgia	United States	30060
10	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
11	Memorial Advanced Cardiovascular Institute	South Bend	Indiana	United States	46601
12	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
13	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
14	Metropolitan Cardiology Consultants PA	Coon Rapids	Minnesota	United States	55433
15	St. Mary's Hospital - Mayo Clinic	Rochester	Minnesota	United States	55902
16	HealthEast St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
17	Bryan LGH	Lincoln	Nebraska	United States	68506
18	Asheville Cardiology Associate PA	Asheville	North Carolina	United States	28803
19	Bethesda North Hospital l TriHealth Hatton Institute	Cincinnati	Ohio	United States	45242
20	Oklahoma Heart Institute	Tulsa	Oklahoma	United States	74104
21	Capital Cardiovascular Associates	Camp Hill	Pennsylvania	United States	17011
22	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
23	Doylestown Cardiology Associates	Doylestown	Pennsylvania	United States	18901
24	Lancaster Heart & Stroke	Lancaster	Pennsylvania	United States	17602
25	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
26	Columbia Heart Clinic	Columbia	South Carolina	United States	29203
27	Stern Cardiovascular	Germantown	Tennessee	United States	38138
28	Saint Thomas Research Institute	Nashville	Tennessee	United States	37205
29	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
30	Saint Luke's Episcopal Hospital - Texas Medical Center	Houston	Texas	United States	77030
31	Baylor Research Institute	Plano	Texas	United States	75093
32	Inova Fairfax Hospital	Fairfax	Virginia	United States	22031
33	Royal Alexandra Hospital	Edmonton	Alberta	Canada
34	Vancouver General Hospital	Vancouver	British Columbia	Canada	V5Z 1M9
35	Victoria Cardiac Arrhythmia Trials Inc	Victoria	British Columbia	Canada
36	Hôpital du Sacre Coeur de Montreal	Montreal	Quebec	Canada
37	McGill University Health Centre	Montreal	Quebec	Canada
38	Montreal Heart Institute	Montreal	Quebec	Canada
39	Institut Universitaire de Cardiologie et de Pneumologie de Québec	Quebec		Canada

Sponsors and Collaborators

• Medtronic Cardiac Rhythm and Heart Failure

Investigators

• Principal Investigator: Bradley P. Knight, MD, FACC, FHRS, Northwestern Memorial Hospital

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 15, 2017
• Study Protocol: Clinical Investigation Plan Version 4 - Aug 18, 2011
• Study Protocol: Clinical Investigation Plan Version 5 - Sep 27, 2013
• Study Protocol: Clinical Investigation Plan Version 6 - Jun 30, 2016

More Information

Publications

None provided.

• Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• ClinicalTrials.gov Identifier: NCT01456949
• Other Study ID Numbers: STOP AF PAS
• First Posted: Oct 21, 2011
• Last Update Posted: Jan 11, 2019
• Last Verified: Dec 1, 2018

• Keywords provided by Medtronic Cardiac Rhythm and Heart Failure: Atrial fibrillation (AF); Paroxysmal atrial fibrillation (PAF); Arrythmias; Cardiac Arrythmias; Cardiac ablation; Cryoablation
• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

Participant Flow

Recruitment Details	The first subjects was enrolled on 26 June 2012 and the first study cryoablation occurred on 28 June 2012. The last subject was enrolled on 21 August 2014 and the final study cryoablation occurred on 14 October 2014. As this was a single arm study, all subjects enrolled were planned to have a cryoablation procedure.

Arm/Group Title	Single Arm
Arm/Group Description	Cryoablation Medtronic Arctic Front® Cardiac CryoAblation System: Cardiac cryoablation to isolate the pulmonary veins using the Arctic Front® CryoAblation System, with point ablation using the Freezor® Max as needed.
Period Title: Enrollment
STARTED	402
Treated	359
Modified Intent to Treat Group (mITT)	354
COMPLETED	365
NOT COMPLETED	37
Period Title: Enrollment
STARTED	365
3-month Follow-up Visit Completed	344
6-month Follow-up Visit Completed	342
12-month Follow-up Visit Completed	325
24-month Follow-up Visit Completed	309
36-month Follow-up Visit Completed	298
COMPLETED	303
NOT COMPLETED	62

Baseline Characteristics

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
Overall Participants	354
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.3 (10.5)
Sex: Female, Male (Count of Participants)
Female	120 33.9%
Male	234 66.1%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.3%
Asian	5 1.4%
Black or African American	1 0.3%
Hispanic or Latino	4 1.1%
Native Hawaiian or Pacific Islander	1 0.3%
White or Caucasian	328 92.7%
Other race	1 0.3%
Unknown/Unreported	13 3.7%

Outcome Measures

1. Primary Outcome

Title	Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) Through 36 Months
Description	Evaluated by assessing the rate of subjects free of chronic treatment failure with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs). Chronic treatment failure is defined as: Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period)
Time Frame	Through 36 months

Outcome Measure Data

Analysis Population Description

Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
Measure Participants	354
Number (95% Confidence Interval) [Percentage of participants]	66.9 18.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Exact binomial
	Comments	Exact binomial p-value is shown, but the confidence intervals reported are calculated from Greenwood's approximation of the standard error.
Method of Estimation	Estimation Parameter	Kaplan-Meier (product-limit) estimator
	Estimated Value	66.9
	Confidence Interval	(2-Sided) 95%; 61.6 to 71.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Safety: Percentage of Participants Experiencing Cryoablation Procedure Events (CPEs) Through 12 Months
Description	Demonstrate safety (through 12 months) of Arctic Front® Cardiac CryoAblation Catheter System, including the Freezor® MAX Cardiac Cryoablation Catheter by assessing the rate of subjects experiencing Cryoablation Procedure Events (CPEs) with paroxysmal atrial fibrillation who have failed one or more Atrial Fibrillation Drugs (AFDs).
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
Measure Participants	354
Number (95% Confidence Interval) [Percentage of participants]	2.3 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Exact binomial
	Comments	Exact binomial p-value is shown, but the confidence intervals reported are calculated from Greenwood's approximation of the standard error.
Method of Estimation	Estimation Parameter	Kaplan-Meier (product-limit) estimator
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 95%; 1.1 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Chronic Safety: Percentage of Participants Free From Major Atrial Fibrillation Events (MAFE) at 1, 2 and 3 Years.
Description	Freedom from Major Atrial Fibrillation Event (MAFE): A MAFE is a serious adverse event (SAE) which has not been categorized as a cryoablation procedure event.
Time Frame	Annually, through 3 years

Outcome Measure Data

Analysis Population Description

Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
Measure Participants	354
Freedom from MAFEs in mITT subjects at 1 year	90.3 25.5%
Freedom from MAFEs in mITT subjects at 2 years	83.2 23.5%
Freedom from MAFEs in mITT subjects at 3 years	77.8 22%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments
	Type of Statistical Test	Other
	Comments	Secondary analyses were exploratory. No formal hypotheses or performance criteria were predefined.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Freedom from MAFE's was estimated using Kaplan-Meier methods.

4. Secondary Outcome

Title	Chronic Effectiveness: Percentage of Participants Free of Chronic Treatment Failure (CTF) at 1 and 2 Years
Description	Freedom from chronic treatment failure, defined as: Documented atrial fibrillation lasting longer than 30 seconds (outside the 90 day blanking period) OR Intervention for atrial fibrillation (except for repeat cryoablation during the 90 day blanking period)
Time Frame	Annually, at 1 and 2 years

Outcome Measure Data

Analysis Population Description

Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.

Arm/Group Title	Modified Intent to Treat Group (mITT)
Arm/Group Description	Enrolled subjects that met all inclusion and no exclusion criteria, and who underwent a study cryoablation procedure.
Measure Participants	354
1 year freedom from CTF	80.4 22.7%
2 year freedom from CTF	72.8 20.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Modified Intent to Treat Group (mITT)
	Comments
	Type of Statistical Test	Other
	Comments	Secondary analyses were exploratory. No formal hypotheses or performance criteria were predefined.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Chronic treatment success was estimated at one and two years using Kaplan-Meier methods.

Adverse Events

Time Frame	All adverse events were collected between subject consent (enrollment) and study completion (3 years post study cryoablation procedure) or study exit.
Arm/Group Title	Treated Group
Arm/Group Description	Enrolled subjects who underwent a study cryoablation procedure whether or not they met all inclusion/exclusion criteria.
All Cause Mortality
	Treated Group
	Affected / at Risk (%)	# Events
Total	5/359 (1.4%)
Serious Adverse Events
	Treated Group
	Affected / at Risk (%)	# Events
Total	145/359 (40.4%)
Blood and lymphatic system disorders
Anaemia	2/359 (0.6%)	2
Lymphadenopathy	1/359 (0.3%)	1
Cardiac disorders
Atrial Fibrillation	65/359 (18.1%)	75
Atrial Flutter	20/359 (5.6%)	20
Coronary Artery Disease	3/359 (0.8%)	5
Cardiac Failure Congestive	4/359 (1.1%)	4
Acute myocardial infarction	3/359 (0.8%)	3
Sinus node dysfunction	3/359 (0.8%)	3
Angina Pectoris	2/359 (0.6%)	2
Angina unstable	2/359 (0.6%)	2
Atrial tachycardia	2/359 (0.6%)	2
Bradycardia	2/359 (0.6%)	2
Pericardial effusion	2/359 (0.6%)	2
Aortic valve stenosis	1/359 (0.3%)	1
Cardiac failure	1/359 (0.3%)	1
Cardiomyopathy	1/359 (0.3%)	1
Mitral valve calcification	1/359 (0.3%)	1
Nodal rhythym	1/359 (0.3%)	1
Pericarditis	1/359 (0.3%)	1
Ventricular tachycardia	1/359 (0.3%)	1
Eye disorders
Glaucoma	1/359 (0.3%)	1
Retinal detachment	1/359 (0.3%)	1
Vitreous detachment	1/359 (0.3%)	1
Gastrointestinal disorders
Inguinal hernia	2/359 (0.6%)	2
Pancreatitis	2/359 (0.6%)	2
Colitis microscopic	1/359 (0.3%)	1
Constipation	1/359 (0.3%)	1
Diverticular perforation	1/359 (0.3%)	1
Gastrointestinal haemmorhage	1/359 (0.3%)	1
Ileus	1/359 (0.3%)	1
Rectal haemmorhage	1/359 (0.3%)	1
Small intestinal obstruction	1/359 (0.3%)	1
Umbilical hernia	1/359 (0.3%)	1
General disorders
Chest pain	2/359 (0.6%)	2
Accidental death	1/359 (0.3%)	1
Catheter site haemorrhage	1/359 (0.3%)	1
Death	1/359 (0.3%)	1
Non-cardiac chest pain	1/359 (0.3%)	1
Hepatobiliary disorders
Cholangitis	1/359 (0.3%)	2
Cholecystitis	1/359 (0.3%)	1
Cholelithiasis	1/359 (0.3%)	1
Post procedural bile leak	1/359 (0.3%)	1
Immune system disorders
Allergy to arthropod sting	1/359 (0.3%)	1
Hypersensitivity	1/359 (0.3%)	1
Infections and infestations
Urinary Tract Infection	5/359 (1.4%)	5
Diverticulitis	2/359 (0.6%)	2
Bronchitis	1/359 (0.3%)	1
Bronchitis viral	1/359 (0.3%)	1
Cellulitis	1/359 (0.3%)	1
Cholecystitis infective	1/359 (0.3%)	1
Clostridium difficile colitis	1/359 (0.3%)	1
Clostridium difficile infection	1/359 (0.3%)	1
Escherichia bacteraemia	1/359 (0.3%)	1
Pneumonia	1/359 (0.3%)	1
Pneumonia bacterial	1/359 (0.3%)	1
Sepsis	1/359 (0.3%)	1
Urosepsis	1/359 (0.3%)	1
Injury, poisoning and procedural complications
Meniscus Injury	4/359 (1.1%)	4
Post procedural haemmorhage	3/359 (0.8%)	3
Fall	1/359 (0.3%)	1
Forearm fracture	1/359 (0.3%)	1
Hip fracture	1/359 (0.3%)	1
Periprosthetic fracture	1/359 (0.3%)	1
Procedural pain	1/359 (0.3%)	1
Spinal compression fracture	1/359 (0.3%)	1
Subdural haematoma	1/359 (0.3%)	1
Toxicity to various agents	1/359 (0.3%)	1
Vascular pseudoaneurysm	1/359 (0.3%)	1
Investigations
CHA2DS2-VASc annual stroke risk moderate	1/359 (0.3%)	1
Metabolism and nutrition disorders
Obesity	1/359 (0.3%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	8/359 (2.2%)	9
Spinal column stenosis	2/359 (0.6%)	2
Cervical spinal stenosis	1/359 (0.3%)	1
Osteonecrosis	1/359 (0.3%)	1
Osteoporosis	1/359 (0.3%)	1
Spinal osteoarthritis	1/359 (0.3%)	1
Trigger finger	1/359 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	2/359 (0.6%)	2
Squamous cell carcinoma	2/359 (0.6%)	2
Basal cell carcinoma	1/359 (0.3%)	1
Bladder adenocarcinoma stage unspecified	1/359 (0.3%)	1
Breast cancer recurrent	1/359 (0.3%)	1
Colon cancer	1/359 (0.3%)	1
Gastric cancer	1/359 (0.3%)	1
Plasma cell leukaemia	1/359 (0.3%)	1
Squamous cell carcinoma of skin	1/359 (0.3%)	1
Thyroid cancer	1/359 (0.3%)	1
Nervous system disorders
Phrenic Nerve Paralysis	3/359 (0.8%)	3
Cerebrovascular accident	1/359 (0.3%)	2
Brain stem haemorrhage	1/359 (0.3%)	1
Carpal tunnel syndrome	1/359 (0.3%)	1
Cauda equina syndrome	1/359 (0.3%)	1
Cerebral Haemmorhage	1/359 (0.3%)	1
Generalised tonic-clonic seizure	1/359 (0.3%)	1
Haemmorhage intracranial	1/359 (0.3%)	1
Migraine	1/359 (0.3%)	1
Multiple sclerosis	1/359 (0.3%)	1
Neuralgia	1/359 (0.3%)	1
Transient global amnesia	1/359 (0.3%)	1
Psychiatric disorders
Mental status changes	1/359 (0.3%)	2
Psychotic disorder	1/359 (0.3%)	1
Renal and urinary disorders
Acute kidney injury	1/359 (0.3%)	1
Calculus ureteric	1/359 (0.3%)	1
Nephrolithiasis	1/359 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Atelectasis	2/359 (0.6%)	2
Dyspnoea	2/359 (0.6%)	2
Pulmonary vein stenosis	2/359 (0.6%)	2
Acute respiratory failure	1/359 (0.3%)	1
Chronic obstructive pulmonary disease	1/359 (0.3%)	1
Haemoptysis	1/359 (0.3%)	1
Pleural effusion	1/359 (0.3%)	1
Pulmonary mass	1/359 (0.3%)	1
Surgical and medical procedures
Colostomy closure	1/359 (0.3%)	1
Knee arthroplasty	1/359 (0.3%)	1
Vascular disorders
Haematoma	2/359 (0.6%)	2
Aortic stenosis	1/359 (0.3%)	1
Hypotension	1/359 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Treated Group
	Affected / at Risk (%)	# Events
Total	70/359 (19.5%)
Cardiac disorders
Atrial fibrillation	70/359 (19.5%)	98

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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