Trial Outcomes & Findings for STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation (NCT NCT03118518)

Last Updated: 2025-02-13

Results Overview

Treatment success after AAD initiation (control arm) or pulmonary vein isolation ablation procedure utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter (treatment arm). Treatment success is the opposite of treatment failure. Treatment failure was defined as any of the following: * Acute procedural failure (treatment arm only). * Documented AF/AT/AFL on ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period (treatment)/AAD optimization period (control arm). Minimum of 30 seconds on ambulatory monitoring or 10 seconds on 12-lead ECG. * Any subsequent AF surgery or ablation in the left atrium. * Any subsequent cardioversion after the 90-day post-ablation blanking period (treatment)/AAD optimization period (control arm). * Class I or III antiarrhythmic drug (or sotalol) use after the 90-day blanking period (treatment arm only).

Recruitment status

COMPLETED

Study phase

Target enrollment

225 participants

Primary outcome timeframe

Randomization to 12 months

Results posted on

2025-02-13

Participant Flow

The first enrollment in the STOP AF First study occurred in the United States on 23-JUN-2017. The final enrollment occurred on 13-MAY-2019.

Of 225 enrolled participants, 210 met inclusion criteria and were randomized to treatment. Of the 15 who exited prior to randomization: 11 did not meet inclusion/exclusion criteria, 2 withdrew, 1 was lost to follow-up and 1 had study enrollment close prior to randomization.

Participant milestones

Participant milestones
Measure	Subjects Randomized to Cryoballoon Catheter Ablation Subjects Randomized to Cryoballoon Catheter Ablation.	Subjects Randomized to Antiarrhythmic Drug Therapy Subjects Randomized to Antiarrhythmic Drug Therapy.
Overall Study STARTED	108	102
Overall Study Subject Treated According to Randomization Assignment	104	99
Overall Study COMPLETED	102	91
Overall Study NOT COMPLETED	6	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Subjects Randomized to Cryoballoon Catheter Ablation Subjects Randomized to Cryoballoon Catheter Ablation.	Subjects Randomized to Antiarrhythmic Drug Therapy Subjects Randomized to Antiarrhythmic Drug Therapy.
Overall Study Early Exit after treatment	2	8
Overall Study Early Exit after randomization but prior to treatment	4	3

Baseline Characteristics

STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects Treated With Cryoballoon Catheter Ablation as Randomized n=104 Participants Subjects Treated with Cryoballoon Catheter Ablation as Randomized.	Subjects Treated With Antiarrhythmic Drug Initiation n=99 Participants Subjects Treated with Antiarrhythmic Drug Initiation.	Total n=203 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	59 Participants n=5 Participants	49 Participants n=7 Participants	108 Participants n=5 Participants
Age, Categorical >=65 years	45 Participants n=5 Participants	50 Participants n=7 Participants	95 Participants n=5 Participants
Age, Continuous	60.4 years STANDARD_DEVIATION 11.2 • n=5 Participants	61.6 years STANDARD_DEVIATION 11.2 • n=7 Participants	61.0 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	42 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	57 Participants n=7 Participants	120 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	97 Participants n=5 Participants	91 Participants n=7 Participants	188 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	94 Participants n=5 Participants	91 Participants n=7 Participants	185 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	104 participants n=5 Participants	99 participants n=7 Participants	203 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to 12 months

Population: Subjects who were received the treatment they were randomized to (modified intent to treat).

Outcome measures

Outcome measures
Measure	Subjects Treated With Cryoballoon Catheter Ablation as Randomized n=104 Participants Subjects Treated with Cryoballoon Catheter Ablation as Randomized.	Subjects Treated With Antiarrhythmic Drug Initiation n=99 Participants Subjects Treated with Antiarrhythmic Drug Initiation.
Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter.	73.7 percentage of participants Interval 64.0 to 81.2	45.0 percentage of participants Interval 34.6 to 54.7

PRIMARY outcome

Timeframe: Randomization to 12 months

Population: Subjects who were cryoablation-treated as randomized (as was pre-specified in both the protocol and Statistical Analysis Plan)

Measured by rate of composite list of serious adverse events in cryoablation-treated as randomized arm. Includes: * TIA within 7 days * Cerebrovascular accident within 7 days * Major bleed that requires transfusion or results in a 20% or greater fall in hematocrit (HCT) within 7 days * Development of a significant pericardial effusion within 30 days. (One that results in hemodynamic compromise, requires elective or urgent pericardiocentesis, or results in a 1-cm or more pericardial effusion as documented by echocardiography). * Symptomatic PV stenosis within 12 months; accompanied by one of the following: 50%-75% reduction in diameter of the pulmonary vein, with symptoms not explained by other conditions; OR \>75% reduction in diameter of the pulmonary vein * MI within 7 days * PNI unresolved at 12 months * AE fistula within 12 months * Major vascular complication that requires intervention, prolongs hospital stay, or requires hospital admission (within 7 days).

Outcome measures

Outcome measures
Measure	Subjects Treated With Cryoballoon Catheter Ablation as Randomized n=104 Participants Subjects Treated with Cryoballoon Catheter Ablation as Randomized.	Subjects Treated With Antiarrhythmic Drug Initiation Subjects Treated with Antiarrhythmic Drug Initiation.
Primary Safety Endpoint - Rate of Composite List of Serious Adverse Events.	1.92 percentage of participants Interval 0.48 to 7.47	—

SECONDARY outcome

Timeframe: Baseline and 12 Months

Population: Subjects treated with cryoballoon catheter ablation as randomized (as was pre-specified in both the protocol and Statistical Analysis Plan) and who had QOL score available at both baseline and 12 month time points.

There are two hypotheses tested in the objective, with separate hypothesis tests for (1) the difference in composite scores from the AFEQT questionnaire taken at baseline and 12 month visits, and (2) for the difference in composite scores for the EQ-5D questionnaire taken at baseline and 12-month visits. Composite AFEQT score is on a scale of zero to one hundred. Higher scores are better. Composite EQ-5D score is on a scale of zero to one. Higher scores are better.

Outcome measures

Outcome measures
Measure	Subjects Treated With Cryoballoon Catheter Ablation as Randomized n=99 Participants Subjects Treated with Cryoballoon Catheter Ablation as Randomized.	Subjects Treated With Antiarrhythmic Drug Initiation Subjects Treated with Antiarrhythmic Drug Initiation.
Quality of Life Scores at Baseline Compared to 12 Months AFEQT composite score (change from baseline to 12 months)	33.3 Score on a scale Interval 29.1 to 37.5	—
Quality of Life Scores at Baseline Compared to 12 Months Composite EQ-5D score (change from baseline to 12 months)	0.04 Score on a scale Interval 0.01 to 0.06	—

SECONDARY outcome

Timeframe: Initial treatment through 12 months.

Population: All subjects treated as randomized (mITT).

Compare health care utilization between the treatment and control arms. There are two hypotheses tested in the objective, with separate hypothesis tests for: (1) the rate of total health care utilization events (cardiovascular-related hospitalizations, emergency room visits, or unscheduled office visits) over 12 months shown as freedom from cardiovascular health care utilization by treatment arm, and (2) freedom from cardioversions (electrical or pharmacological) over 12 months by treatment arm.

Outcome measures

Outcome measures
Measure	Subjects Treated With Cryoballoon Catheter Ablation as Randomized n=104 Participants Subjects Treated with Cryoballoon Catheter Ablation as Randomized.	Subjects Treated With Antiarrhythmic Drug Initiation n=99 Participants Subjects Treated with Antiarrhythmic Drug Initiation.
Healthcare Utilization Freedom from Cardiovascular health care utilization.	69.9 percentage of participants Interval 60.0 to 77.8	53.5 percentage of participants Interval 42.8 to 63.1
Healthcare Utilization Freedom from Cardioversion	97.1 percentage of participants Interval 91.3 to 99.1	92.4 percentage of participants Interval 84.8 to 96.3

Adverse Events

Randomized and Treated With Cryoablation

Serious events: 16 serious events

Other events: 8 other events

Deaths: 0 deaths

Randomized and Treated With Antiarrhythmic Drugs

Serious events: 14 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Randomized and Treated With Cryoablation n=104 participants at risk Subjects Treated with Cryoballoon Catheter Ablation as Randomized.	Randomized and Treated With Antiarrhythmic Drugs n=99 participants at risk Subjects Treated with Antiarrhythmic Drug Initiation as Randomized
Cardiac disorders Atrial fibrillation	7.7% 8/104 • Number of events 12 • During or after treatment initiation through study completion (12 months visit). Adverse events occurring during the study were continuously monitored and collected. The following adverse events were collected starting at the time subjects signed the Informed Consent Form through the duration of the subject's participation in the study: * All procedure related AEs * All cryoablation system related AEs * All AAD related AEs * All cardiovascular related AEs * All Serious Adverse Events (SAEs), regardless of relatedness	16.2% 16/99 • Number of events 20 • During or after treatment initiation through study completion (12 months visit). Adverse events occurring during the study were continuously monitored and collected. The following adverse events were collected starting at the time subjects signed the Informed Consent Form through the duration of the subject's participation in the study: * All procedure related AEs * All cryoablation system related AEs * All AAD related AEs * All cardiovascular related AEs * All Serious Adverse Events (SAEs), regardless of relatedness

Additional Information

Erika Pouliot

Medtronic

Phone: 17635261270

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place