Trial Outcomes & Findings for A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation (NCT NCT00523978)

Last Updated: 2018-10-16

Results Overview

Acute Procedural Success was defined as a demonstration of electrical isolation in ≥ 3 Pulmonary Veins (PVs) at the conclusion of the first protocol-defined cryoablation procedure. APS was decided at the end of the procedure the mean time was calculated for the time frame.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

245 participants

Primary outcome timeframe

371.4 Minutes (Average)

Results posted on

2018-10-16

Participant Flow

Investigators at 26 sites in the United States and Canada, enrolled and randomized a total of 245 study subjects, during the 21 months trial period, between 10 October 2006 and 30 June 2008.

Participant milestones

Participant milestones
Measure	Cryoablation an experimental group receiving cryoablation and, optionally, a previously failed Atrial Fibrillation Drug.3 Subjects withdrew consent 5 subjects were a screen failure. Therefore N=163 for Experimental group.	Standard Treatment With Drugs Only a control group receiving only an Atrial Fibrillation Drug. 4 Subject withdrew consent and 1 subject was a screen failure. Therefore- Control Treatment group N= 82.
Overall Study STARTED	171	87
Overall Study COMPLETED	162	79
Overall Study NOT COMPLETED	9	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Cryoablation an experimental group receiving cryoablation and, optionally, a previously failed Atrial Fibrillation Drug.3 Subjects withdrew consent 5 subjects were a screen failure. Therefore N=163 for Experimental group.	Standard Treatment With Drugs Only a control group receiving only an Atrial Fibrillation Drug. 4 Subject withdrew consent and 1 subject was a screen failure. Therefore- Control Treatment group N= 82.
Overall Study Withdrawal by Subject	3	7
Overall Study Screen Failures	5	1
Overall Study Death	1	0

Baseline Characteristics

A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cryoablation n=163 Participants an experimental group receiving cryoablation and, optionally, a previously failed Atrial Fibrillation Drug.3 Subjects withdrew consent 5 subjects were a screen failure. Therefore N=163 for Experimental group.	Standard Treatment With Drugs Only n=82 Participants a control group receiving only an Atrial Fibrillation Drug. 4 Subject withdrew consent and 1 subject was a screen failure. Therefore- Control Treatment group N= 82.	Total n=245 Participants Total of all reporting groups
Age, Continuous	56.7 years STANDARD_DEVIATION 0.73 • n=5 Participants	56.4 years STANDARD_DEVIATION 1.04 • n=7 Participants	56.6 years STANDARD_DEVIATION 0.6 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	18 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	64 Participants n=7 Participants	189 Participants n=5 Participants
Region of Enrollment United States	123 participants n=5 Participants	63 participants n=7 Participants	186 participants n=5 Participants
Region of Enrollment Canada	40 participants n=5 Participants	19 participants n=7 Participants	59 participants n=5 Participants

PRIMARY outcome

Timeframe: 371.4 Minutes (Average)

Population: Subjects evaluated were from the modified Intent to Treat subset (mITT)or subjects that were enrolled, randomized and received treatment.

Outcome measures

Outcome measures
Measure	Cryoablation n=163 Participants Experimental group or group that were cryoablated with Arctic Front® Cardiac CryoAblation Catheter System, including the FlexCath® Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter	Standard Treatment With Drugs Only A control group receiving only an Atrial Fibrillation Drug who have not previously failed a AF study drug.
Acute Procedural Success (APS)	160 participants	—

PRIMARY outcome

Timeframe: 12 month follow up period

Population: This section includes data for subjects who were randomized, received treatment and were followed through 12-Months post randomized treatment regardless of AF Drug usage. Subjects who experienced Acute Procedural Failure in the Experimental group were not included in this analysis of post-procedural failure causes.

Subjects that did not have or were free of CTF. CTF was defined as the occurence of an Atrial Fibrillation (AF) intervention, use of non-study AF drug therapy, or the occurence of detectable AF which is is defined as an episode of AF, documented in a tracing, and lasting more than 30 seconds, occurring during a Non Blanked Follow-up Period.

Outcome measures

Outcome measures
Measure	Cryoablation n=163 Participants Experimental group or group that were cryoablated with Arctic Front® Cardiac CryoAblation Catheter System, including the FlexCath® Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter	Standard Treatment With Drugs Only n=82 Participants A control group receiving only an Atrial Fibrillation Drug who have not previously failed a AF study drug.
Freedom From Chronic Treatment Failure (CTF)	117 participants	6 participants

PRIMARY outcome

Timeframe: 12 months

Population: The mITT population consisted of all subjects, who were enrolled, randomized and received treatment

Treatment Success was defined as Acute Procedure Success (APS) and freedom from Chronic Treatment Failure (CTF) for Experimental Subjects, and freedom from CTF for Control Subjects. Under this pre-specified definition of Treatment Success, Experimental Subjects must have had APS and remained free of CTF during the 12-month follow-up duration, while Control Subjects must have remained free of CTF during the 12-month follow-up duration.

Outcome measures

Outcome measures
Measure	Cryoablation n=163 Participants Experimental group or group that were cryoablated with Arctic Front® Cardiac CryoAblation Catheter System, including the FlexCath® Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter	Standard Treatment With Drugs Only n=82 Participants A control group receiving only an Atrial Fibrillation Drug who have not previously failed a AF study drug.
Treatment Success	114 participants Interval 62.3 to 76.9	6 participants Interval 2.7 to 15.2

PRIMARY outcome

Timeframe: 12 Months

Population: mITT set included all subjects (82 CS, 163 ES) who were enrolled, randomized, and received treatment.

Subjects that did not have or were free of MAFEs. MAFEs were serious adverse events categorized as cardiovascular death, myocardial infarction, stroke, or hospitalization for AF recurrence/ablation, flutter ablation, embolic events, heart failure, hemorrhage or anti-arrhythmic drug treatment.

Outcome measures

Outcome measures
Measure	Cryoablation n=163 Participants Experimental group or group that were cryoablated with Arctic Front® Cardiac CryoAblation Catheter System, including the FlexCath® Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter	Standard Treatment With Drugs Only n=82 Participants A control group receiving only an Atrial Fibrillation Drug who have not previously failed a AF study drug.
Freedom From Major Atrial Fibrillation Events (MAFEs)	158 participants	75 participants

PRIMARY outcome

Timeframe: To end of ablation procedure

Population: Data for subjects who were randomized to the Experimental group and received cryoablation therapy were included in this analysis. All CPEs reported in the Experimental group were included in the analysis regardless of their association with the first or a repeat cryoablation.

Subjects that had CPEs. CPEs were device- or procedure-related serious adverse events (SAE) categorized as access site complications, cardiac damage, pulmonary vein (PV) stenosis, embolic complications, arrhythmias, unresolved phrenic nerve palsy and death.

Outcome measures

Outcome measures
Measure	Cryoablation n=163 Participants Experimental group or group that were cryoablated with Arctic Front® Cardiac CryoAblation Catheter System, including the FlexCath® Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter	Standard Treatment With Drugs Only A control group receiving only an Atrial Fibrillation Drug who have not previously failed a AF study drug.
Cryoablation Procedure Events (CPEs)	5 participants	—

Adverse Events

Cryoablation

Serious events: 20 serious events

Other events: 19 other events

Deaths: 0 deaths

Standard Treatment With Drugs Only

Serious events: 12 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Linda Nelson, RN, BSN, MBA - AF Solutions Clinical Operations Director

Medtronic AF Solutions

Phone: (763)526-2891

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Cryoablation n=163 participants at risk Experimental group or subjects that were cryoablated with Arctic Front® Cardiac CryoAblation Catheter System, including the FlexCath® Steerable Sheath and Freezor® MAX Cardiac Cryoablation Catheter	Standard Treatment With Drugs Only n=65 participants at risk；n=82 participants at risk A control group receiving only an Atrial Fibrillation Drug who have not previously failed a AF study drug.
Cardiac disorders Atrial Fibrillation	8.6% 14/163 • Number of events 14 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	24.6% 16/65 • Number of events 16 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Cardiac disorders Atrial Flutter	11.0% 18/163 • Number of events 18 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	15.4% 10/65 • Number of events 10 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Cardiac disorders Bradycardia	0.00% 0/163 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
General disorders Fatigue	7.4% 12/163 • Number of events 12 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	13.8% 9/65 • Number of events 9 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
General disorders Chest Pain	5.5% 9/163 • Number of events 9 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
General disorders Chest Discomfort	2.5% 4/163 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	12.3% 8/65 • Number of events 8 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
General disorders Asthenia	1.2% 2/163 • Number of events 2 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Nervous system disorders Headache	10.4% 17/163 • Number of events 17 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	16.9% 11/65 • Number of events 11 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Nervous system disorders Dizziness	9.2% 15/163 • Number of events 15 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	13.8% 9/65 • Number of events 9 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Respiratory, thoracic and mediastinal disorders Cough	11.7% 19/163 • Number of events 19 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	10.8% 7/65 • Number of events 7 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.3% 7/163 • Number of events 7 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	10.8% 7/65 • Number of events 7 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Gastrointestinal disorders Nausea	5.5% 9/163 • Number of events 9 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	13.8% 9/65 • Number of events 9 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Infections and infestations Bronchitis	6.1% 10/163 • Number of events 10 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	4.6% 3/65 • Number of events 3 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Musculoskeletal and connective tissue disorders Back Pain	3.7% 6/163 • Number of events 6 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Musculoskeletal and connective tissue disorders Arthralgia	1.8% 3/163 • Number of events 3 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Vascular disorders Hypertension	3.7% 6/163 • Number of events 6 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Vascular disorders Hypotension	1.8% 3/163 • Number of events 3 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	7.7% 5/65 • Number of events 5 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.
Investigations international Normalised Ratio Increased	1.2% 2/163 • Number of events 2 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.	6.2% 4/65 • Number of events 4 • All pharmacologic and ablative treatments and arrhythmic disease adverse events on study subjects were followed through 12 months of follow-up. All serious adverse events (SAE) were adjudicated by the CEC to the protocol definitions.