SMART-SF Radiofrequency Ablation Safety Study

• Sponsor: Biosense Webster, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02359890
• Collaborator: (none)
• Enrollment: 165
• Locations: 17
• Arm: 1
• Actual Duration (Months): 20.3
• Patients Per Site: 9.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This is a prospective safety assessment of the study device during radiofrequency (RF) ablation treatment of patients with drug refractory symptomatic atrial fibrillation (SMART-SF).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Device: THERMOCOOL® SMARTTOUCH® (RF ablation treatment)	Phase 3

Detailed Description

The purpose of this study is to demonstrate the safety of the study device in the treatment of drug refractory symptomatic paroxysmal atrial fibrillation (PAF) during standard electrophysiology mapping and RF ablation procedures.

Study Design

• Study Type: Interventional
• Actual Enrollment: 165 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective Safety Assessment of the THERMOCOOL® SMARTTOUCH® SF Family of Contact Force Sensing Catheters for the Radiofrequency Ablation Treatment of Drug Refractory Symptomatic Paroxysmal Atrial Fibrillation
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Nov 8, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Group Pulmonary vein isolation by RF ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)	Device: THERMOCOOL® SMARTTOUCH® (RF ablation treatment); Radiofrequency Ablation Treatment; Other Names: Pulmonary vein isolation

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Early Onset Primary Adverse Events [Seven days post ablation procedure]

   Early onset is defined as within 7 days of the atrial fibrillation (AF) ablation procedure. Primary adverse events (AE) include Death, Myocardial infarction (MI), Pulmonary vein (PV) stenosis, Diaphragmatic paralysis, Atrio-esophageal fistula, Transient Ischemic Attack (TIA), Stroke / Cerebrovascular accident (CVA), Thromboembolism, Pericarditis, Cardiac Tamponade / Perforation, Pneumothorax, Major Vascular Access Complications / Bleeding, Pulmonary edema (Respiratory Insufficiency), and Heart block.

Secondary Outcome Measures

1. Percentage of Participants With Non-Primary Serious Adverse Events (SAEs) [Up to 30 days post Procedure]

   This secondary safety endpoint includes non-primary serious adverse events (SAEs) within 7 days post-procedure and serious adverse events from 8 days to 30 days post-procedure

2. Percentage of Participants With Acute Success [End of procedure]

   Acute success is defined as confirmation of entrance block in all Pulmonary veins (PV).

3. Effectiveness Endpoint: Freedom From Documented Atrial Fibrillation (AF)/Atrial Tachycardia (AT)/Atrial Flutter (AFL) [12 months]

   The freedom from documented AF/AT/AFL based on electrocardiographic data

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Symptomatic paroxysmal atrial fibrillation (AF) who have had at least one AF episode electrocardiographically documented within one (1) year prior to enrollment and a physician's note indicating recurrent, self-terminating AF. Electrocardiographic documentation may include, but is not limited to, electrocardiogram (ECG), transtelephonic monitor (TTM), Holter monitor (HM), or telemetry strip

• Failed at least one antiarrhythmic drug (AAD) (class I or III, or atrioventricular (AV) nodal blocking agents such as beta blockers and calcium channel blockers) as evidenced by recurrent symptomatic AF, or intolerable to the AAD

• Age 18 years or older

Exclusion Criteria:

• Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause

• Previous surgical or catheter ablation for atrial fibrillation

• Amiodarone at any time during the past 3 months

• Any percutaneous coronary intervention (PCI), cardiac surgery, or valvular cardiac surgical or percutaneous procedure (e.g., ventriculotomy, atriotomy, and valve repair or replacement and presence of a prosthetic valve) within the past 2 months

• Any carotid stenting or endarterectomy

• Coronary artery bypass graft (CABG) surgery within the past 6 months

• AF episodes lasting >7 days

• Documented left atrial (LA) thrombus on imaging

• LA size >50 mm

• Left ventricular ejection fraction (LVEF) < 40%

• Contraindication to anticoagulation (heparin or warfarin)

• History of blood clotting or bleeding abnormalities

• MI within the past 2 months

• Documented thromboembolic event (including transient ischemic attack (TIA)) within the past 12 months

• Rheumatic Heart Disease

• Uncontrolled heart failure or New York Heart Association (NYHA) function class III or IV

• Awaiting cardiac transplantation or other cardiac surgery within the next 12 months

• Unstable angina

• Acute illness or active systemic infection or sepsis

• Diagnosed atrial myxoma

• Presence of implanted implantable cardioverter defibrillator (ICD)

• Significant pulmonary disease, (eg, restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces chronic symptoms

• Significant congenital anomaly or medical problem that in the opinion of the investigator would preclude enrollment in this study

• Women who are pregnant (as evidenced by pregnancy test if pre-menopausal)

• Enrollment in an investigational study evaluating another device, biologic, or drug

• Presence of intramural thrombus, tumor or other abnormality that precludes vascular access, or manipulation of the catheter

• Presence of a condition that precludes vascular access

• Life expectancy or other disease processes likely to limit survival to less than 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scripps Green Hospital	San Diego	California	United States	92037
2	Sharp Memorial Hospital	San Diego	California	United States	92123
3	Santa Barbara Cottage Hospital	Santa Barbara	California	United States	93105
4	Providence Saint John's Health Center / Pacific Heart Institute	Santa Monica	California	United States	90404
5	JFK Medical Center	Atlantis	Florida	United States	33462
6	Florida Hospital Orlando	Orlando	Florida	United States	32803
7	Emory Saint Joseph's Hospital	Atlanta	Georgia	United States	30342
8	Central Baptist Hospital	Lexington	Kentucky	United States	40503
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
11	Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55407
12	NYU Langone Medical Center	New York	New York	United States	10003
13	Penn-State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
14	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Texas Cardiac Arrhythmia Research Foundation - St. David's	Austin	Texas	United States	78705
16	HeartPlace	Bedford	Texas	United States	76021
17	Memorial Hermann Medical Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Biosense Webster, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Sponsor website

Publications

• Natale A, Reddy VY, Monir G, Wilber DJ, Lindsay BD, McElderry HT, Kantipudi C, Mansour MC, Melby DP, Packer DL, Nakagawa H, Zhang B, Stagg RB, Boo LM, Marchlinski FE. Paroxysmal AF catheter ablation with a contact force sensing catheter: results of the prospective, multicenter SMART-AF trial. J Am Coll Cardiol. 2014 Aug 19;64(7):647-56. doi: 10.1016/j.jacc.2014.04.072.
• Oza SR, Hunter TD, Biviano AB, Dandamudi G, Herweg B, Patel AM, Pollak SJ, Wang H, Fishel RS. Acute safety of an open-irrigated ablation catheter with 56-hole porous tip for radiofrequency ablation of paroxysmal atrial fibrillation: analysis from 2 observational registry studies. J Cardiovasc Electrophysiol. 2014 Aug;25(8):852-858. doi: 10.1111/jce.12403. Epub 2014 Apr 9.

• Responsible Party: Biosense Webster, Inc.
• ClinicalTrials.gov Identifier: NCT02359890
• Other Study ID Numbers: SMART-SF; STSF-162
• First Posted: Feb 10, 2015
• Last Update Posted: Aug 20, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Biosense Webster, Inc.: Interventional; Radiofrequency ablation; Paroxysmal Atrial Fibrillation
• Additional relevant MeSH terms: Atrial Fibrillation

Study Results

Participant Flow

Recruitment Details	This study enrolled 165 subjects at 17 clinical sites in the U.S. over approximately 5 months. The first subject was enrolled on March 30, 2015 and the last subject was enrolled on September 9, 2015. The last ablation procedure was on September 17, 2015. The last 1-month follow-up visit occurred on November 3, 2015.

Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Family of Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
Period Title: Overall Study
STARTED	165
Safety Population	159
mITT Population	155
Per-Protocol (PP) Population	155
COMPLETED	155
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Family of Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
Overall Participants	164
Age (Years) [Mean (Standard Deviation) ]
Age (Years)	62.7 (10.44)
Sex: Female, Male (Count of Participants)
Female	69 42.1%
Male	95 57.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 1.2%
Not Hispanic or Latino	155 94.5%
Unknown or Not Reported	7 4.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 0.6%
Native Hawaiian or Other Pacific Islander	1 0.6%
Black or African American	2 1.2%
White	159 97%
More than one race	0 0%
Unknown or Not Reported	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Early Onset Primary Adverse Events
Description	Early onset is defined as within 7 days of the atrial fibrillation (AF) ablation procedure. Primary adverse events (AE) include Death, Myocardial infarction (MI), Pulmonary vein (PV) stenosis, Diaphragmatic paralysis, Atrio-esophageal fistula, Transient Ischemic Attack (TIA), Stroke / Cerebrovascular accident (CVA), Thromboembolism, Pericarditis, Cardiac Tamponade / Perforation, Pneumothorax, Major Vascular Access Complications / Bleeding, Pulmonary edema (Respiratory Insufficiency), and Heart block.
Time Frame	Seven days post ablation procedure

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat (mITT) population was used, which consisted of enrolled subjects who met the eligibility criteria and had the study catheter inserted.

Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
Measure Participants	155
Number (95% Confidence Interval) [Percentage of participants]	2.6 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THERMOCOOL SMARTTOUCH® SF Catheters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants with events
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; 0.7 to 6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 2-sided 95% confidence interval is derived using the exact Clopper-Pearson interval.

2. Secondary Outcome

Title	Percentage of Participants With Non-Primary Serious Adverse Events (SAEs)
Description	This secondary safety endpoint includes non-primary serious adverse events (SAEs) within 7 days post-procedure and serious adverse events from 8 days to 30 days post-procedure
Time Frame	Up to 30 days post Procedure

Outcome Measure Data

Analysis Population Description

Safety Population (SP), which is defined as the enrolled subjects who had the study catheter inserted.

Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
Measure Participants	159
Patients with SAE within 7 days post procedure	3.1 1.9%
Patients with SAE during 8-30 days post-procedure	0.6 0.4%

3. Secondary Outcome

Title	Percentage of Participants With Acute Success
Description	Acute success is defined as confirmation of entrance block in all Pulmonary veins (PV).
Time Frame	End of procedure

Outcome Measure Data

Analysis Population Description

Safety Population (SP), which is defined as the enrolled subjects who had the study catheter inserted.

Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
Measure Participants	159
Number (95% Confidence Interval) [Percentage of participants]	96.2 58.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THERMOCOOL SMARTTOUCH® SF Catheters
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of patient with acute success
	Estimated Value	96.2
	Confidence Interval	(2-Sided) 95%; 92.0 to 98.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 2-sided 95% confidence interval is derived using the exact Clopper-Pearson interval

4. Secondary Outcome

Title	Effectiveness Endpoint: Freedom From Documented Atrial Fibrillation (AF)/Atrial Tachycardia (AT)/Atrial Flutter (AFL)
Description	The freedom from documented AF/AT/AFL based on electrocardiographic data
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Effectiveness per Protocol Population, which is defined as enrolled subjects who underwent RF ablation procedure with study catheter and completed the 12 month visit.

Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
Measure Participants	76
Number (95% Confidence Interval) [Percentage of Participants]	75 45.7%

Adverse Events

Time Frame	30 days post procedure
Arm/Group Title	THERMOCOOL SMARTTOUCH® SF Family of Catheters
Arm/Group Description	Pulmonary vein isolation by radiofrequency (RF) ablation treatment with the THERMOCOOL® SMARTTOUCH® SF family of contact force sensing catheters (study device)
All Cause Mortality
	THERMOCOOL SMARTTOUCH® SF Family of Catheters
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	THERMOCOOL SMARTTOUCH® SF Family of Catheters
	Affected / at Risk (%)	# Events
Total	9/159 (5.7%)
Cardiac disorders
Atrial fibrillation with rapid ventricular response	1/159 (0.6%)	1
Cardiac Tamponade	2/159 (1.3%)	2
Eye disorders
Hospitalization due to transient neurological symptoms	1/159 (0.6%)	1
Gastrointestinal disorders
Abdominal pain/nausea/constipation	1/159 (0.6%)	1
General disorders
Thromboembolism	1/159 (0.6%)	1
Infections and infestations
Sepsis due to urinary tract and upper respiratory infection	1/159 (0.6%)	1
Nervous system disorders
Transient Ischemic Attack	1/159 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration pneumonia	1/159 (0.6%)	1
Septic shock due to pneumonia with abscess	1/159 (0.6%)	1
Other (Not Including Serious) Adverse Events
	THERMOCOOL SMARTTOUCH® SF Family of Catheters
	Affected / at Risk (%)	# Events
Total	31/159 (19.5%)
Cardiac disorders
Pericarditis	1/159 (0.6%)	1
Atrial Flutter	4/159 (2.5%)	4
Atrial Tachycardia	1/159 (0.6%)	1
Paroxysmal SVT	1/159 (0.6%)	1
Atypical left atrial flutter	1/159 (0.6%)	1
Shock	1/159 (0.6%)	1
Gastrointestinal disorders
Nausea	1/159 (0.6%)	1
General disorders
Globus feeling in pharynx	1/159 (0.6%)	1
Chest pressure	1/159 (0.6%)	1
Catheter site edema	1/159 (0.6%)	1
Fatigue	6/159 (3.8%)	6
Radiating chest pain	2/159 (1.3%)	2
Chest pain/discomfort	1/159 (0.6%)	1
Infections and infestations
Cellulitis	1/159 (0.6%)	1
UTI	1/159 (0.6%)	1
Tooth infection	1/159 (0.6%)	1
Injury, poisoning and procedural complications
Dizziness	1/159 (0.6%)	1
Poison ivy exposure	1/159 (0.6%)	1
Metabolism and nutrition disorders
Fluid retention	1/159 (0.6%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/159 (0.6%)	1
Nervous system disorders
Numbness in feet	1/159 (0.6%)	1
Lightheadedness	1/159 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/159 (0.6%)	1
Shortness of breath	2/159 (1.3%)	2
Dyspnea	1/159 (0.6%)	1
Vascular disorders
Groin hematoma	3/159 (1.9%)	3
Hypotension	1/159 (0.6%)	1

Limitations/Caveats

Additional data pertaining to this study expected to be submitted in August 2018. Re-monitoring of safety event data is in progress.

More Information

Certain Agreements

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

There IS an agreement between the Principal Investigator (PI)/Institution and the Sponsor (or its agents) that restricts the PI's rights to discuss, present or publish trial results after the trial is completed. Please contact Biosense Webster, Inc. for additional information.