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出境医 / 临床实验 / Cryoballoon Pulmonary Vein Isolation vs. Radiofrequency Pulmonary Vein Isolation With Additional Right Atrial Linear Ablation for Paroxysmal Atrial Fibrillation: Prospective Randomized Trial (CRAPAF Trial)

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

Study Description
Brief Summary:
Cryoballoon ablation is proven to be effective in pulmonary vein isolation in patients with paroxysmal atrial fibrillation, and it can reduce the procedure time compared to conventional radiofrequency (RF) catheter ablation. Recently, high-power short-duration RF ablation has been known to reduce procedure time remarkably, and it can eliminate extra-pulmonary vein foci, which cannot be treated by Cryoballoon ablation. The aim of this study is to compare Cryoballoon ablation and high-power short-duration RF ablation in patients with paroxysmal atrial fibrillation in terms of the efficacy and the safety in a prospective randomized trial.

Condition or disease Intervention/treatment Phase
Paroxysmal Atrial Fibrillation Procedure: Cryoballoon Pulmonary Vein isolation Procedure: Radiofrequency Pulmonary Vein isolation and Additional Right Atrial linear ablation Not Applicable

Detailed Description:

A. Study design

  1. Prospective randomization (cryoballoon PV isolation group vs. Radiofrequency Pulmonary Vein isolation and Additional Right Atrial linear ablation) (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: 330 (165 per group)
  3. Rhythm FU : 2012 ACC/AHA/ESC guidelines (Holter monitoring at the baseline, 3,6 month, and thereafter every 6 months to 24 month, then 1 year; ECG if the patient has any symptom)
  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.

B. Progress and rhythm/ECG follow-up

  1. To be performed in accordance with the 2012 ACC/AHA/HRS guidelines for AF management
  2. Follow-up at 1 weeks, 3,6 months, and thereafter every 6-month after procedure.
  3. Rhythm control at 3,6 months, and thereafter every 6-month follow-up with Holter
  4. 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 All the patients will be followed-up at 1 weeks, 3, 6 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 3, 6 months, and thereafter 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.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 330 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cryoballoon Pulmonary Vein Isolation vs. Radiofrequency Pulmonary Vein Isolation With Additional Right Atrial Linear Ablation for Paroxysmal Atrial Fibrillation: Prospective Randomized Trial (CRAPAF Trial)
Actual Study Start Date : April 3, 2019
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: Cryoballoon Pulmonary Vein isolation
  1. Pulmonary vein isolation will be performed using a cryoballoon catheter.
  2. Esophageal temperature will be monitored to prevent esophageal injury.
  3. A 28mm second or third cryoballoon catheter will be used.
  4. Esophageal temperature will be monitored to prevent esophageal injury.
  5. Cryoablation will be performed for 180 secs at -45°C or below on condition that the pulmonary vein is occluded with a cryoballoon.
  6. CMAP (compound motor action potential) monitoring will be done to avoid phrenic nerve damage during the freezing of the right superior pulmonary vein.
  7. The procedure and cryoablation times will be evaluated.
  8. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
Procedure: Cryoballoon Pulmonary Vein isolation
  1. Pulmonary vein isolation will be performed using a cryoballoon catheter.
  2. Esophageal temperature will be monitored to prevent esophageal injury.
  3. A 28mm second or third cryoballoon catheter will be used.
  4. Esophageal temperature will be monitored to prevent esophageal injury.
  5. Cryoablation will be performed for 180 secs at -45°C or below on condition that the pulmonary vein is occluded with a cryoballoon.
  6. CMAP (compound motor action potential) monitoring will be done to avoid phrenic nerve damage during the freezing of the right superior pulmonary vein.
  7. The procedure and cryoablation times will be evaluated.
  8. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.

Active Comparator: Radiofrequency Pulmonary Vein isolation
  1. Pulmonary vein isolation will be performed using a radiofrequency catheter.
  2. Additional cavo-tricuspid isthmus ablation will be performed with a radiofrequency catheter.
  3. Additional superior vena cava-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 radiofrequency ablation will be followed.
  5. Evaluated the procedure and radiofrequency ablation time.
  6. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
Procedure: Radiofrequency Pulmonary Vein isolation and Additional Right Atrial linear ablation
  1. Pulmonary vein isolation will be performed using a radiofrequency catheter.
  2. Additional cavo-tricuspid isthmus ablation will be performed with a radiofrequency catheter.
  3. Additional superior vena cava-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 radiofrequency ablation will be followed.
  5. Evaluated the procedure and radiofrequency ablation time.
  6. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.

Outcome Measures
Primary Outcome Measures :
  1. Safety evaluation: Procedure-related cardiac complication rate [ Time Frame: within 30 days post procedure ]
    including open cardiac surgery, cerebral infarction, pericardial effusion or cardiac tamponade, hematoma in the inguinal puncture site and vascular complications within 30 days post procedure

  2. Efficacy evaluation: clinical recurrence rate [ Time Frame: Within 1 year after 3 months of procedure ]
    Defined as atrial fibrillation or atrial tachycardia > 30 sec after 3 months within 1 year; based on the 2012 ACC/AHA/HRS guidelines, 24-hour Holter ECG monitoring will be performed at 3 month and every 6 months, and ECG and monitoring with a Holter or an event recorder will be performed at any time if the patient complains of symptoms


Secondary Outcome Measures :
  1. Comparison of procedure time [ Time Frame: immediate after procedure ]
  2. Comparison of ablation time [ Time Frame: immediate after procedure ]
  3. Comparison of hospitalization period [ Time Frame: immediate after procedure ]
  4. Comparison of re-hospitalization rate after the procedure [ Time Frame: immediate after procedure ]
  5. Comparison of re-hospitalization rate after the procedure [ Time Frame: 12 months after procedure ]
  6. Comparison of number of electrical cardioversion after the procedure [ Time Frame: immediate after procedure ]
  7. Comparison of number of electrical cardioversion after the procedure [ Time Frame: 12 months after procedure ]
  8. Major cardiovascular event rate - death, myocardial infarction, coronary angioplasty, and re-hospitalization for arrhythmia and heart failure [ Time Frame: immediate after procedure and 12 months after procedure ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Patient with paroxysmal atrial fibrillation who is scheduled for ablation procedure and ≥20 and ≤80 years of age
  • 2. Left atrium size < 45mm
  • 3. paroxysmal atrial fibrillation that is recurrence during antiarrhythmic drug treatment or is not able to use an antiarrhythmic drug.
  • 4. Patient who is indicated for anticoagulation therapy (for prevention of cerebral infarction)

Exclusion Criteria:

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

Contacts
Layout table for location contacts
Contact: Hui-Nam Pak, M.D, Ph.D. 82-2-2228-8459 hnpak@yuhs.ac

Locations
Layout table for location information
Korea, Republic of
Severance Cardiovascular Hospital, Yonsei University Health System Recruiting
Seoul, Korea, Republic of, 120-752
Contact: Hui-Nam Pak, M.D., Ph.D.    82-2-2228-8459    hnpak@yuhs.ac   
Sponsors and Collaborators
Yonsei University
Investigators
Layout table for investigator information
Principal Investigator: Hui-Nam Pak, M.D, Ph.D. Severance Hospital
Tracking Information
First Submitted Date  ICMJE April 14, 2019
First Posted Date  ICMJE April 19, 2019
Last Update Posted Date January 5, 2021
Actual Study Start Date  ICMJE April 3, 2019
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • Safety evaluation: Procedure-related cardiac complication rate [ Time Frame: within 30 days post procedure ]
    including open cardiac surgery, cerebral infarction, pericardial effusion or cardiac tamponade, hematoma in the inguinal puncture site and vascular complications within 30 days post procedure
  • Efficacy evaluation: clinical recurrence rate [ Time Frame: Within 1 year after 3 months of procedure ]
    Defined as atrial fibrillation or atrial tachycardia > 30 sec after 3 months within 1 year; based on the 2012 ACC/AHA/HRS guidelines, 24-hour Holter ECG monitoring will be performed at 3 month and every 6 months, and ECG and monitoring with a Holter or an event recorder will be performed at any time if the patient complains of symptoms
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • Comparison of procedure time [ Time Frame: immediate after procedure ]
  • Comparison of ablation time [ Time Frame: immediate after procedure ]
  • Comparison of hospitalization period [ Time Frame: immediate after procedure ]
  • Comparison of re-hospitalization rate after the procedure [ Time Frame: immediate after procedure ]
  • Comparison of re-hospitalization rate after the procedure [ Time Frame: 12 months after procedure ]
  • Comparison of number of electrical cardioversion after the procedure [ Time Frame: immediate after procedure ]
  • Comparison of number of electrical cardioversion after the procedure [ Time Frame: 12 months after procedure ]
  • Major cardiovascular event rate - death, myocardial infarction, coronary angioplasty, and re-hospitalization for arrhythmia and heart failure [ Time Frame: immediate after procedure and 12 months after procedure ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cryoballoon Pulmonary Vein Isolation vs. Radiofrequency Pulmonary Vein Isolation With Additional Right Atrial Linear Ablation for Paroxysmal Atrial Fibrillation: Prospective Randomized Trial (CRAPAF Trial)
Official Title  ICMJE Cryoballoon Pulmonary Vein Isolation vs. Radiofrequency Pulmonary Vein Isolation With Additional Right Atrial Linear Ablation for Paroxysmal Atrial Fibrillation: Prospective Randomized Trial (CRAPAF Trial)
Brief Summary Cryoballoon ablation is proven to be effective in pulmonary vein isolation in patients with paroxysmal atrial fibrillation, and it can reduce the procedure time compared to conventional radiofrequency (RF) catheter ablation. Recently, high-power short-duration RF ablation has been known to reduce procedure time remarkably, and it can eliminate extra-pulmonary vein foci, which cannot be treated by Cryoballoon ablation. The aim of this study is to compare Cryoballoon ablation and high-power short-duration RF ablation in patients with paroxysmal atrial fibrillation in terms of the efficacy and the safety in a prospective randomized trial.
Detailed Description

A. Study design

  1. Prospective randomization (cryoballoon PV isolation group vs. Radiofrequency Pulmonary Vein isolation and Additional Right Atrial linear ablation) (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: 330 (165 per group)
  3. Rhythm FU : 2012 ACC/AHA/ESC guidelines (Holter monitoring at the baseline, 3,6 month, and thereafter every 6 months to 24 month, then 1 year; ECG if the patient has any symptom)
  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.

B. Progress and rhythm/ECG follow-up

  1. To be performed in accordance with the 2012 ACC/AHA/HRS guidelines for AF management
  2. Follow-up at 1 weeks, 3,6 months, and thereafter every 6-month after procedure.
  3. Rhythm control at 3,6 months, and thereafter every 6-month follow-up with Holter
  4. 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 All the patients will be followed-up at 1 weeks, 3, 6 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 3, 6 months, and thereafter 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Atrial Fibrillation
Intervention  ICMJE
  • Procedure: Cryoballoon Pulmonary Vein isolation
    1. Pulmonary vein isolation will be performed using a cryoballoon catheter.
    2. Esophageal temperature will be monitored to prevent esophageal injury.
    3. A 28mm second or third cryoballoon catheter will be used.
    4. Esophageal temperature will be monitored to prevent esophageal injury.
    5. Cryoablation will be performed for 180 secs at -45°C or below on condition that the pulmonary vein is occluded with a cryoballoon.
    6. CMAP (compound motor action potential) monitoring will be done to avoid phrenic nerve damage during the freezing of the right superior pulmonary vein.
    7. The procedure and cryoablation times will be evaluated.
    8. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
  • Procedure: Radiofrequency Pulmonary Vein isolation and Additional Right Atrial linear ablation
    1. Pulmonary vein isolation will be performed using a radiofrequency catheter.
    2. Additional cavo-tricuspid isthmus ablation will be performed with a radiofrequency catheter.
    3. Additional superior vena cava-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 radiofrequency ablation will be followed.
    5. Evaluated the procedure and radiofrequency ablation time.
    6. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
Study Arms  ICMJE
  • Experimental: Cryoballoon Pulmonary Vein isolation
    1. Pulmonary vein isolation will be performed using a cryoballoon catheter.
    2. Esophageal temperature will be monitored to prevent esophageal injury.
    3. A 28mm second or third cryoballoon catheter will be used.
    4. Esophageal temperature will be monitored to prevent esophageal injury.
    5. Cryoablation will be performed for 180 secs at -45°C or below on condition that the pulmonary vein is occluded with a cryoballoon.
    6. CMAP (compound motor action potential) monitoring will be done to avoid phrenic nerve damage during the freezing of the right superior pulmonary vein.
    7. The procedure and cryoablation times will be evaluated.
    8. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
    Intervention: Procedure: Cryoballoon Pulmonary Vein isolation
  • Active Comparator: Radiofrequency Pulmonary Vein isolation
    1. Pulmonary vein isolation will be performed using a radiofrequency catheter.
    2. Additional cavo-tricuspid isthmus ablation will be performed with a radiofrequency catheter.
    3. Additional superior vena cava-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 radiofrequency ablation will be followed.
    5. Evaluated the procedure and radiofrequency ablation time.
    6. Rhythm follow-up will be performed after the procedure in accordance with the aforementioned study design.
    Intervention: Procedure: Radiofrequency Pulmonary Vein isolation and Additional Right Atrial linear ablation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 16, 2019)
330
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2024
Estimated Primary Completion Date March 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 1. Patient with paroxysmal atrial fibrillation who is scheduled for ablation procedure and ≥20 and ≤80 years of age
  • 2. Left atrium size < 45mm
  • 3. paroxysmal atrial fibrillation that is recurrence during antiarrhythmic drug treatment or is not able to use an antiarrhythmic drug.
  • 4. Patient who is indicated for anticoagulation therapy (for prevention of cerebral infarction)

Exclusion Criteria:

  • 1. Patients with persistent or permanent atrial fibrillation
  • 2. Atrial fibrillation associated with severe cardiac malformation or a structural heart disease that is hemodynamically affected
  • 3. Patients with severe renal impairment or CT imaging difficulty using contrast media
  • 4. Patients with a past history of radiofrequency ablation for atrial fibrillation or other cardiac surgery
  • 5. Patients with active internal bleeding
  • 6. Patients with contraindications for anticoagulation therapy(for prevention of cerebral infarction) and antiarrhythmic drugs
  • 7. Patients with valvular atrial fibrillation (mitral stenosis >grade 2, mechanical valve, mitral valvuloplasty)
  • 8. Patients with a severe comorbid disease
  • 9. Expected survival < 1 year
  • 10. Drug addicts or alcoholics
  • 11. Patients who cannot read the consent form (illiterates, foreigners, etc.)
  • 12. Other patients who are judged by the principal or sub-investigator to be ineligible for participation in this clinical study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hui-Nam Pak, M.D, Ph.D. 82-2-2228-8459 hnpak@yuhs.ac
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03920917
Other Study ID Numbers  ICMJE 4-2019-0139
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yonsei University
Study Sponsor  ICMJE Yonsei University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Hui-Nam Pak, M.D, Ph.D. Severance Hospital
PRS Account Yonsei University
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP