Cryoballoon Pulmonary Vein Isolation vs. Cryoballoon Pulmonary Vein Isolation With Additional Right Atrial Linear Ablation for Persistent Atrial Fibrillation (CRARAL Trial)

August 29, 2023 updated by: Yonsei University

Cryoballoon Pulmonary Vein Isolation vs. Cryoballoon Pulmonary Vein Isolation With Additional Right Atrial Linear Ablation for Persistent Atrial Fibrillation: Prospective Randomized Trial (CRARAL Trial)

Cryoballoon ablation is proven to be effective in pulmonary vein isolation in patients with paroxysmal atrial fibrillation. However, it is not certain that cryoablation is effective and safe in patients with persistent atrial fibrillation, because of higher chance of recurrence compared to paroxysmal atrial fibrillation. The aim of this study is to evaluate the efficacy and safety of cryoballoon pulmonary vein isolation vs. cryoballoon pulmonary vein isolation with additional right atrial linear ablation for paroxysmal atrial fibrillation in a prospective randomized trial

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A. Study design

  1. Prospective randomization (cryoballoon PV isolation group vs. cryoballoon PV isolation group with additional RA linear ablation group) (Using the Python program, a random number module is imported with the import random syntax, and the random number table for the two groups is created.)
  2. Target number of subjects: 278 (138 per group)
  3. Rhythm FU : ECG during every visit (1, 3, 6, and 12 months, and then every 6 months thereafter or upon the recurrence of symptoms after AFCA) and 24-h Holter monitor recording at 3 and 6 months and every 6 months thereafter.
  4. Anticoagulant therapy followed by 2014 ACC/AHA/ESC guidelines
  5. All complications in each group will be evaluated including the re-hospitalization rate, major cardiovascular event, and mortality rate.

Cryoballoon PV isolation group

  1. Pulmonary vein isolation will be performed using a cryoballoon catheter.
  2. Esophageal temperature will be monitored to prevent esophageal injury.
  3. A 28mm cryoballoon catheter will be used.
  4. Cryoablation will be performed for 180 secs at -30ºC or below on condition that the pulmonary vein is occluded with a cryoballoon.
  5. CMAP (compound motor action potential) monitoring will be done to avoid phrenic nerve damage during the freezing of the right superior pulmonary vein.
  6. The procedure and ablation times will be evaluated.
  7. The procedure will be completed without checking any other trigger came from beyond pulmonary vein after the administration of isoproterenol
  8. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.

Cryoballoon PV isolation with Additional RA linear ablation group

  1. Pulmonary vein isolation will be performed using a cryoballoon catheter as the same as cryoballoon PV isolation group.
  2. Additional cavo-tricuspid isthmus ablation will be performed with a radiofrequency catheter.
  3. Additional SVC-right atrial septal linear ablation will be performed with a radiofrequency catheter.
  4. If any other trigger came from beyond pulmonary vein is detected after the administration of isoproterenol, additional local RF ablation will be followed.
  5. The procedure and ablation times will be evaluated.
  6. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.

B. Progress and rhythm/ECG follow-up

  1. To be performed in accordance with the 2012 ACC/AHA/HRS guidelines for AF management
  2. Followed up for a minimum of 12 months after ablation.
  3. Outpatient clinic visits regularly at 1, 3, 6, and 12 months, and then every 6 months thereafter or upon the recurrence of symptoms after AFCA Rhythm control at 2 months, and thereafter every 6-month follow-up with
  4. ECG during every visit and 24-h Holter monitor recording at 3 and 6 months and every 6 months thereafter.
  5. If the patient complains of symptoms, ECG will be performed at any time, and rhythm follow-up will be carried out with a Holter or event recorder.

C. Follow-up Patients were followed up for a minimum of 12 months after ablation. All the patients will be followed-up at 1, 3, 6, and 12 months, and thereafter every 6 months. If the patient shows any symptom within the clinical study period, patient will visit the outpatient clinic. ECG will be performed at every outpatient visits, and 24-hour Holter or event recording will be performed every 6 months for 2 years, and every year after 2 years (2012 Heart Rhythm Society/EHRA/European Cardiac Arrhythmia Society Expert Consensus Statement guidelines). If atrial fibrillation or atrial tachycardia lasting more than 30 seconds is observed in 12-lead ECG or Holter, it will be evaluated as recurrence. Recurrence within 3 months after the procedure will be classified as early recurrence, and that after 3 months will be classified as clinical recurrence.

9. Observation Items • Clinical Test Items and Observation Method A. Disease name, age, gender, weight, height, disease duration B. Evaluation of comorbid structural heart disease pattern C. Evaluation of clinically significant comorbid disease pattern D. Imaging quantitative assessment (All the examinations will be performed according to the need for treatment, regardless of the purpose of the study, and no additional imaging tests will be performed for study purposes.)

  1. Echocardiography: Ejection fraction, diastolic function index, atrial size, ventricular size, atrial volume
  2. 3D CT scan: Atrial size, ventricular size, atrial volume, and pericardial fat volume (This examination is indispensable for the safety of the procedure and for the use of 3D equipment in catheter ablation for atrial fibrillation in all clinical studies. The analysis of the atrial size, pericardial fat volume, etc. will be utilized for the purpose of risk assessment for recurrence-related factor detection and future recurrence risk. In other words, the purpose is to provide better treatment for patients at a higher level.) E. Hemodynamic quantitative evaluation: Measurement of atrial pressure before and after the procedure

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
195

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Severance Cardiovascular Hospital, Yonsei University Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient with persistent atrial fibrillation who is scheduled for ablation procedure
  • ≥20 and ≤80 years of age
  • LA size ≤ 45mm
  • Patient who is indicated for anticoagulation therapy(for prevention of cerebral infarction) and antiarrhythmic drug

Exclusion Criteria:

  • Patients with paroxysmal or permanent atrial fibrillation
  • Atrial fibrillation associated with severe cardiac malformation or a structural heart disease that is hemodynamically affected
  • Patients with severe renal impairment or CT imaging difficulty using contrast media
  • Patients with a past history of radiofrequency ablation for atrial fibrillation or other cardiac surgery
  • Patients with active internal bleeding
  • Patients with contraindications for anticoagulation therapy (for prevention of cerebral infarction) and antiarrhythmic drugs
  • Patients with valvular atrial fibrillation (mitral stenosis >grade 2, mechanical valve)
  • Patients with a severe comorbid disease
  • Expected survival < 1 year
  • Drug addicts or alcoholics
  • Patients who cannot read the consent form (illiterates, foreigners, etc.)
  • Other patients who are judged by the principal or sub-investigator to be ineligible for participation in this clinical study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Cryoballoon PV isolation group
  1. Pulmonary vein isolation will be performed using a cryoballoon catheter.
  2. Esophageal temperature will be monitored to prevent esophageal injury.
  3. A 28mm cryoballoon catheter will be used.
  4. Cryoablation will be performed for 180 secs at -30 C or below on condition that the pulmonary vein is occluded with a cryoballoon.
  5. CMAP (compound motor action potential) monitoring will be done to avoid phrenic nerve damage during the freezing of the right superior pulmonary vein.
  6. The procedure and ablation times will be evaluated.
  7. The procedure will be completed without checking any other trigger came from beyond pulmonary vein after the administration of isoproterenol
  8. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
Procedure: Cryoballoon PV isolation group
  1. Prospective randomization (cryoballoon PV isolation group vs. cryoballoon PV isolation group with additional RA linear ablation group) (Using the Python program, a random number module is imported with the import random syntax, and the random number table for the two groups is created.)
  2. Target number of subjects: 278 (138 per group)
  3. Rhythm FU : ECG during every visit (1, 3, 6, and 12 months, and then every 6 months thereafter or upon the recurrence of symptoms after AFCA) and 24-h Holter monitor recording at 3 and 6 months and every 6 months thereafter.
  4. Anticoagulant therapy followed by 2014 ACC/AHA/ESC guidelines
  5. All complications in each group will be evaluated including the re-hospitalization rate, major cardiovascular event, and mortality rate.
Experimental: Cryoballoon PV isolation w/ RA linear ablation group
  1. Pulmonary vein isolation will be performed using a cryoballoon catheter as the same as cryoballoon PV isolation group.
  2. Additional cavo-tricuspid isthmus ablation will be performed with a radiofrequency catheter.
  3. Additional SVC-right atrial septal linear ablation will be performed with a radiofrequency catheter.
  4. If any other trigger came from beyond pulmonary vein is detected after the administration of isoproterenol, additional local RF ablation will be followed.
  5. The procedure and ablation times will be evaluated.
  6. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
Procedure: Cryoballoon PV isolation with Additional RA linear ablation group
  1. Prospective randomization (cryoballoon PV isolation group vs. cryoballoon PV isolation group with additional RA linear ablation group) (Using the Python program, a random number module is imported with the import random syntax, and the random number table for the two groups is created.)
  2. Target number of subjects: 278 (138 per group)
  3. Rhythm FU : ECG during every visit (1, 3, 6, and 12 months, and then every 6 months thereafter or upon the recurrence of symptoms after AFCA) and 24-h Holter monitor recording at 3 and 6 months and every 6 months thereafter.
  4. Anticoagulant therapy followed by 2014 ACC/AHA/ESC guidelines
  5. All complications in each group will be evaluated including the re-hospitalization rate, major cardiovascular event, and mortality rate.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recurrence of any atrial arrhythmia
Time Frame: up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
Recurrence of any atrial arrhythmia (Defined as atrial fibrillation, atrial tachycardia, or atrial flutter lasting at least 30 seconds after a 3-month post-procedure blanking period
up to 24 months with a minimum of 12 months follow up after a single ablation procedure.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Procedure time
Time Frame: immediate after procedure
immediate after procedure
Anti-arrhythmic drug use after a 3-month blanking period
Time Frame: up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
Recurrence of any atrial arrhythmia lasting at least 30 seconds occurring after a 3-month blanking period or anti-arrhythmic drug use after a 3-months blanking period
Time Frame: up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
Number of patients with recurrence as atrial fibrillation
Time Frame: up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
Number of patients with recurrence as atrial tachycardia/flutter
Time Frame: up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
Procedural complications
Time Frame: immediate after procedure
immediate after procedure
Proportion of cardioversion performed among patients with the recurrence of atrial arrhythmia.
Time Frame: up to 24 months with a minimum of 12 months follow up after a single ablation procedure.
up to 24 months with a minimum of 12 months follow up after a single ablation procedure.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yonsei University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Hui-Nam Pak, Yonsei University Health System, Severance Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 7, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 5, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 29, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 4-2018-0734

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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