Atrial FibrillationSTOP AF FirstNCT03118518
STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation
A study testing Cryoablation and Antiarrhythmic drug in people with Atrial Fibrillation and Atrial Fibrillation New Onset, run by Medtronic Cardiac Ablation Solutions at 24 sites in United States.
Trial summary
To provide data demonstrating the safety and effectiveness of the Arctic Front Advance™ Cardiac CryoAblation Catheter for the treatment of recurrent symptomatic paroxysmal atrial fibrillation, without the requirement that the subjects be drug refractory. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atrial Fibrillation, Atrial Fibrillation New Onset
- What is being tested?
- Cryoablation and Antiarrhythmic drug
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 24 sitesUnited States
- Study dates
- 23 Jun 2017to 25 Jun 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A diagnosis of symptomatic paroxysmal AF with the following documentation: (1) physician's note indicating recurrent self- terminating AF or paroxysmal AF; and (2) any ECG documented AF within 6 months prior to enrollment.
- Age 18-80
Who cannot join
- History of AF treatment with class I or III antiarrhythmic drug, including sotalol, with the intention to prevent an AF recurrence. However, patients pretreated with above AAD for less than 7 days with the intention to convert an AF episode are allowed.
- Prior persistent AF (cardioversion after 48 hours or continuous AF that is sustained >7 days)
- Left atrial diameter greater than 5.0 cm
- Prior left atrial ablation or left atrial surgical procedure
- Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function)
- Body mass index (BMI) >35 kg/m2
Show all 29Show fewer
- Presence of any pulmonary vein stents
- Known presence of any pre-existing pulmonary vein stenosis
- Pre-existing hemidiaphragmatic paralysis
- Presence of any cardiac valve prosthesis
- Moderate or severe mitral valve regurgitation or stenosis
- Any cardiac surgery, myocardial infarction, percutaneous coronary intervention/ percutaneous transluminal coronary angioplasty or coronary artery stenting which occurred during the 90 day interval preceding the date the subject signed the Informed Consent Form
- Unstable angina
- New York Heart Association (NYHA) class III or IV congestive heart failure and/or known left ventricular ejection fraction (LVEF) less than 45%
- Diagnosis of primary pulmonary hypertension
- Rheumatic heart disease
- Thrombocytosis, thrombocytopenia
- Contraindication to anticoagulation therapy
- Active systemic infection
- Hypertrophic cardiomyopathy
- Cryoglobulinemia
- Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, obstructive sleep apnea, and acute alcohol toxicity.
- Any cerebral ischemic event (strokes or transient ischemic attacks) which occurred during the 180 day interval preceding the date the subject signed the Informed Consent Form, or any known unresolved complications from previous stroke/transient ischemic attack
- Existing thrombus
- Pregnancy
- Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed.
- 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
- Patients with contraindications to a Holter monitor
- Unwilling or unable to comply fully with study procedures and follow-up
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
Lehigh Valley Health
Allentown, Pennsylvania, 18105
Alaska Heart Institute
Anchorage, Alaska, 50266-8209
University of Michigan Health System - University Hospital
Ann Arbor, Michigan, 50266-8209
Our Lady of the Lake Office of Research
Baton Rouge, Louisiana, 50266-8209
Grandview Medical Center
Birmingham, Alabama, 35243
Cleveland Clinic
Cleveland, Ohio, 44195-0001
Ohio State University
Columbus, Ohio, 43210
Geisinger Medical Center
Danville, Pennsylvania, 17821
Spectrum Health Hospitals
Grand Rapids, Michigan, 49503
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Krannert Institute of Cardiology
Indianapolis, Indiana, 46202
Bryan Heart
Lincoln, Nebraska, 07450-2726
Wellstar Research Institute
Marietta, Georgia, 30060
Aurora Cardiovascular Services
Milwaukee, Wisconsin, 50266-8209
Southcoast Health System
New Bedford, Massachusetts, 02740
Hoag Hospital Newport Beach
Newport Beach, California, 92663
Integris Baptist Medical Center, Inc.
Oklahoma City, Oklahoma, 73112-4418
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
The Valley Hospital
Ridgewood, New Jersey, 07450-2726
HealthEast Saint Josephs Hospital
Saint Paul, Minnesota, 55102-1062
Tallahassee Research Institute Inc
Tallahassee, Florida, 32308-4646
BayCare Medical Group Cardiology
Tampa, Florida, 33607
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010-3017
Iowa Heart Center
West Des Moines, Iowa, 50266-8209
About this study
To provide data demonstrating the safety and effectiveness of the Arctic Front Advance™ Cardiac CryoAblation Catheter for the treatment of recurrent symptomatic paroxysmal atrial fibrillation, without the requirement that the subjects be drug refractory.
Read the detailed description
Subjects with paroxysmal atrial fibrillation with no history of treatment with anti-arrhythmic drugs are randomized 1:1 to either an anti-arrhythmic drug or pulmonary vein isolation using the cryoballoon catheter.
- Conditions
- Atrial Fibrillation, Atrial Fibrillation New Onset
- Being tested
- Cryoablation, Antiarrhythmic drug
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CryoablationDevice
Also called ArcticFront Advance Cardiac CryoAblation Catheter
Pulmonary vein isolation via ablation with cryoballoon catheter
Antiarrhythmic drugDrug
Antiarrhythmic drug initiation
| Study group | Role | What they receive |
|---|---|---|
| Anti-arrhythmic drug | Active comparator | Not described Receives: Drug: Antiarrhythmic drug |
| Cryoablation | Experimental | Not described Receives: Device: Cryoablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter.
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).
Measured: Randomization to 12 months
Primary Safety Endpoint - Rate of Composite List of Serious Adverse Events.
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).
Measured: Randomization to 12 months
Secondary outcomes (2)
Quality of Life Scores at Baseline Compared to 12 Months
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.
Measured: Baseline and 12 Months
Healthcare Utilization
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.
Measured: Initial treatment through 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2017
- Study start23 Jun 2017
- Primary completion25 Jun 2020
- Study completion25 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Medtronic Cardiac Ablation SolutionsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medtronic Cardiac Ablation Solutions
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Oussama Wazni, MD, Principal investigator, The Cleveland ClinicGopi Dandamudi, MD, Principal investigator, Franciscan Heart & Vascular Associates at St. JosephSteve Nissen, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03118518
- Sponsor's protocol ID
- MDT16012AFS001
- Acronym
- STOP AF First
- Status last verified
- Feb 2025
- First submitted
- 4 Apr 2017
- Last updated
- 13 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Andrade JG, Moss JWE, Kuniss M, Sadri H, Wazni O, Sale A, Ismyrloglou E, Chierchia GB, Kaplon R, Mealing S, Bainbridge J, Bromilow T, Lane E, Khaykin Y. The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation. Can J Cardiol. 2024 Apr;40(4):576-584. doi: 10.1016/j.cjca.2023.11.019. Epub 2023 Nov 23.
PubMed 38007219Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, Niebauer M, Makati K, Halperin B, Gauri A, Morales G, Shao M, Cerkvenik J, Kaplon RE, Nissen SE; STOP AF First Trial Investigators. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):316-324. doi: 10.1056/NEJMoa2029554. Epub 2020 Nov 16.
PubMed 33197158
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation
- ClinicalTrials.gov ID
- NCT03118518
- Acronym / sponsor ID
- STOP AF First / MDT16012AFS001
- Conditions
- Atrial Fibrillation, Atrial Fibrillation New Onset
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 225 participants (actual)
- Lead sponsor
- Medtronic Cardiac Ablation SolutionsIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2017 (actual)
- Primary completion
- 25 Jun 2020 (actual)
- Study completion
- 25 Jun 2020 (actual)
- First posted
- 18 Apr 2017 (actual)
- Results
- Posted 11 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To provide data demonstrating the safety and effectiveness of the Arctic Front Advance™ Cardiac CryoAblation Catheter for the treatment of recurrent symptomatic paroxysmal atrial fibrillation, without the requirement that the subjects be drug refractory.
Detailed description
Subjects with paroxysmal atrial fibrillation with no history of treatment with anti-arrhythmic drugs are randomized 1:1 to either an anti-arrhythmic drug or pulmonary vein isolation using the cryoballoon catheter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anti-arrhythmic drug | Active comparator | Drug: Antiarrhythmic drug |
| Cryoablation | Experimental | Device: Cryoablation |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- A diagnosis of symptomatic paroxysmal AF with the following documentation: (1) physician's note indicating recurrent self- terminating AF or paroxysmal AF; and (2) any ECG documented AF within 6 months prior to enrollment.
- Age 18-80
Key exclusion criteria (29 listed)
- History of AF treatment with class I or III antiarrhythmic drug, including sotalol, with the intention to prevent an AF recurrence. However, patients pretreated with above AAD for less than 7 days with the intention to convert an AF episode are allowed.
- Prior persistent AF (cardioversion after 48 hours or continuous AF that is sustained >7 days)
- Left atrial diameter greater than 5.0 cm
- Prior left atrial ablation or left atrial surgical procedure
- Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CryoablationAlso: ArcticFront Advance Cardiac CryoAblation CatheterPulmonary vein isolation via ablation with cryoballoon catheter | Device | Cryoablation |
| Antiarrhythmic drugAntiarrhythmic drug initiation | Drug | Anti-arrhythmic drug |
Primary outcome
Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter.
Time frame: Randomization to 12 months
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).
Primary Safety Endpoint - Rate of Composite List of Serious Adverse Events.
Time frame: Randomization to 12 months
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).
2 secondary outcomes
Quality of Life Scores at Baseline Compared to 12 Months
Time frame: Baseline and 12 Months
Healthcare Utilization
Time frame: Initial treatment through 12 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38007219Andrade JG, Moss JWE, Kuniss M, Sadri H, Wazni O, Sale A, Ismyrloglou E, Chierchia GB, Kaplon R, Mealing S, Bainbridge J, Bromilow T, Lane E, Khaykin Y. The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation. Can J Cardiol. 2024 Apr;40(4):576-584. doi: 10.1016/j.cjca.2023.11.019. Epub 2023 Nov 23.
- Derived from this study: PubMed 33197158Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, Niebauer M, Makati K, Halperin B, Gauri A, Morales G, Shao M, Cerkvenik J, Kaplon RE, Nissen SE; STOP AF First Trial Investigators. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):316-324. doi: 10.1056/NEJMoa2029554. Epub 2020 Nov 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oussama Wazni, MD principal investigator
The Cleveland Clinic
Gopi Dandamudi, MD principal investigator
Franciscan Heart & Vascular Associates at St. Joseph
Steve Nissen, MD principal investigator
The Cleveland Clinic
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cryoablation and Antiarrhythmic drug in people with Atrial Fibrillation and Atrial Fibrillation New Onset, run by Medtronic Cardiac Ablation Solutions at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter. (time frame: Randomization to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03118518, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2025; AzTrials last refreshed its copy on 7 Nov 2026.