NCT03118518: STOP AF First

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

Completed NA Results posted Last updated 13 February 2025

What this trial tests

NA trial testing Cryoablation in Atrial Fibrillation in 225 participants. Completed in 25 June 2020.

Timeline

23 June 2017

Primary endpoint
25 June 2020

25 June 2020

Quick facts

Lead sponsor	Medtronic Cardiac Ablation Solutions
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	225
Start date	23 June 2017
Primary completion	25 June 2020
Estimated completion	25 June 2020
Sites	24 locations across United States

Drugs / interventions tested

• Cryoablation — full drug profile →
• Antiarrhythmic drug — full drug profile →

Conditions studied

• Atrial Fibrillation — all drugs for Atrial Fibrillation →
• Atrial Fibrillation New Onset — all drugs for Atrial Fibrillation New Onset →

Sponsor

Medtronic Cardiac Ablation Solutions — full company profile →

Who can join

Adults 18 to 80, any sex, with Atrial Fibrillation or Atrial Fibrillation New Onset. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter. Primary · 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 s

Group	Value	95% CI
Subjects Treated With Cryoballoon Catheter Ablation as Randomized	73.7	64.0 – 81.2
Subjects Treated With Antiarrhythmic Drug Initiation	45.0	34.6 – 54.7

Primary Safety Endpoint - Rate of Composite List of Serious Adverse Events. Primary · 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

Group	Value	95% CI
Subjects Treated With Cryoballoon Catheter Ablation as Randomized	1.92	0.48 – 7.47

Quality of Life Scores at Baseline Compared to 12 Months Secondary · Baseline and 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.

AFEQT composite score (change from baseline to 12 months)

Group	Value	95% CI
Subjects Treated With Cryoballoon Catheter Ablation as Randomized	33.3	29.1 – 37.5

Composite EQ-5D score (change from baseline to 12 months)

Group	Value	95% CI
Subjects Treated With Cryoballoon Catheter Ablation as Randomized	0.04	0.01 – 0.06

Healthcare Utilization Secondary · Initial treatment through 12 months.

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.

Freedom from Cardiovascular health care utilization.

Group	Value	95% CI
Subjects Treated With Cryoballoon Catheter Ablation as Randomized	69.9	60.0 – 77.8
Subjects Treated With Antiarrhythmic Drug Initiation	53.5	42.8 – 63.1

Freedom from Cardioversion

Group	Value	95% CI
Subjects Treated With Cryoballoon Catheter Ablation as Randomized	97.1	91.3 – 99.1
Subjects Treated With Antiarrhythmic Drug Initiation	92.4	84.8 – 96.3

Adverse events — posted to ClinicalTrials.gov

Time frame: During or after treatment initiation through study completion (12 months visit).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Randomized and Treated With Cryoablation

Serious: 16/104 (15%)

Deaths: 0/104

Randomized and Treated With Antiarrhythmic Drugs

Serious: 14/99 (14%)

Deaths: 0/99

Serious adverse events (31 terms)

Reaction	System	Randomized and Treated Wit…	Randomized and Treated Wit…
Atrial fibrillation	Cardiac disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Syncope	Nervous system disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Angina unstable	Cardiac disorders	—	—
Bradycardia	Cardiac disorders	—	—
Cardiac sarcoidosis	Cardiac disorders	—	—
Palpitations	Cardiac disorders	—	—
Pericardial effusion	Cardiac disorders	—	—
Pericarditis	Cardiac disorders	—	—
Ventricular tachyarrhythmia	Cardiac disorders	—	—
Chest pain	General disorders	—	—
Stenosis	General disorders	—	—
Appendicitis	Infections and infestations	—	—
Influenza	Infections and infestations	—	—
Heart rate increased	Investigations	—	—
Fluid overload	Metabolism and nutrition disorders	—	—
Obesity	Metabolism and nutrition disorders	—	—
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	—	—
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	—	—
Hepatic cyst	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Encephalopathy	Nervous system disorders	—	—
Migraine	Nervous system disorders	—	—
Nephrolithiasis	Renal and urinary disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Randomized and Treated Wit…	Randomized and Treated Wit…
Atrial fibrillation	Cardiac disorders	—	—

Most-reported serious reactions: Atrial fibrillation, Osteoarthritis, Syncope, Acute myocardial infarction, Angina unstable, Bradycardia, Cardiac sarcoidosis, Palpitations.

Data from ClinicalTrials.gov NCT03118518 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.
   Wazni OM, Dandamudi G, Sood N, Hoyt R, et al · · 2021 · cited 454× · PMID 33197158 · DOI 10.1056/nejmoa2029554
2. Economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from an English National Health Service perspective.
   Paisey J, Moss J, Andrade J, Kuniss M, et al · · 2024 · cited 9× · PMID 38238026 · DOI 10.1136/openhrt-2023-002423
3. An economic evaluation of first-line cryoballoon ablation vs antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a U.S. Medicare perspective.
   Wazni O, Moss J, Kuniss M, Andrade J, et al · · 2023 · cited 8× · PMID 37744940 · DOI 10.1016/j.hroo.2023.07.007
4. The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation.
   Andrade JG, Moss JWE, Kuniss M, Sadri H, et al · · 2024 · cited 7× · PMID 38007219 · DOI 10.1016/j.cjca.2023.11.019
5. Trends and predictors of early ablation for Atrial Fibrillation in a Nationwide population under age 65: a retrospective observational study.
   D'Angelo RN, Khanna R, Yeh RW, Goldstein L, et al · · 2020 · cited 7× · PMID 32252637 · DOI 10.1186/s12872-020-01446-9
6. A danish healthcare-focused economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation.
   Hansen ML, Moss JWE, Tønnesen J, Johansen ML, et al · · 2024 · cited 3× · PMID 39014312 · DOI 10.1186/s12872-024-04024-5
7. An economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a German healthcare payer perspective.
   Kuniss M, Hillcoat L, Moss J, Straube F, et al · · 2024 · cited 2× · PMID 39593158 · DOI 10.1186/s12913-024-11967-0
8. Redefining the Standard for Atrial Fibrillation: A Patient-centric Report.
   Lundqvist CB, Pürerfellner H, White A, Schilling R. · · 2021 · PMID 33859732 · DOI 10.15420/ecr.2021.16.s1