Cryoballoon Ablation as First Line Treatment of Atrial Flutter (CRAFT)

Cryoballoon Pulmonary Vein Isolation as First Line Treatment for Typical Atrial Flutter

Current guidelines recommend radiofrequency catheter ablation of the cavotricuspid isthmus as treatment for symptomatic/drug-refractory atrial flutter, in spite of the fact that recurrences of flutter and incidence of post-ablation atrial fibrillation are common.

In this study, the investigators assess the hypothesis that the use of cryoballoon Pulmonary Vein Isolation ('novel' treatment) to achieve the electrical disconnection between the pulmonary veins and the heart will lead to higher rates of freedom from abnormal heart rhythms (atrial flutter, atrial fibrillation, or atrial tachycardia) and more improved quality of life than treatment using heat energy (radiofrequency ablation) directed at the cavotricuspid isthmus ('conventional treatment').

Study Overview

• Status: Completed
• Conditions: Atrial Flutter Typical
• Intervention / Treatment: Procedure: Radiofrequency ablation of CTI; Procedure: Cryoballoon PVI

Detailed Description

Atrial flutter and atrial fibrillation are believed to share the same initiating triggers in the form of pulmonary vein ectopy. Cavo-tricuspid isthmus-dependent atrial flutter almost always results from short bursts of antecedent atrial fibrillation. Radiofrequency (RF) ablation of the cavo-tricuspid isthmus (CTI) is the current accepted first-line treatment for atrial flutter, although post-ablation atrial fibrillation commonly occurs, even in the absence of pre-existing atrial fibrillation.

Cryoballoon Pulmonary Vein Isolation (PVI) has become an established treatment for atrial fibrillation. In patients with both atrial flutter and fibrillation, PVI alone has been shown to control both types of atrial arrhythmia, with no benefit derived from supplemental RF CTI ablation.

This study aims to demonstrate that standalone cryoballoon PVI for typical atrial flutter without RF CTI ablation will lead to a significant difference in preventing recurrence of atrial arrhythmia compared to radiofrequency ablation of the CTI, and should be offered as first-line therapy.

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • University Hospital Basel
  • Bern, Switzerland
    • University Hospital Inselspital Bern
• United Kingdom
  • Leeds, United Kingdom
    • Leeds Teaching Hospitals NHS Trust
  • Liverpool, United Kingdom, L14 3PE
    • Liverpool Heart and Chest Hospital NHS Foundation Trust
  • Manchester, United Kingdom, M23 9LT
    • Manchester University NHS Foundation Trust, Wythenshawe Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • South Tees Hospitals NHS Foundation Trust, James Cook University Hospital
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • The Newcastle Upon Tyne Hospital NHS Foundation Trust, Freeman Hospital
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
  • Plymouth, United Kingdom
    • University Hospitals Plymouth NHS trust
  • Cambridge
    • Papworth Everard, Cambridge, United Kingdom, CB23 3RE
      • Royal Papworth Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age 18-80 years
• 2. Patients referred for catheter ablation for typical atrial flutter. The atrial flutter may be either persistent or paroxysmal, with at least one episode having been documented on 12-lead ECG. In the view of the treating physician, the ECG morphology should be compatible with a CTI-dependent circuit, either counterclockwise or clockwise.

Exclusion Criteria:

• 1. Any evidence of previously documented atrial fibrillation
• 2. Previous cavo-tricuspid isthmus ablation or atrial fibrillation ablation
• 3. Atrial flutter documented solely on Ambulatory monitoring
• 4. Atrial flutter morphology on ECG suggestive of a left atrial flutter
• 5. History of atrial flutter with 1:1 atrioventricular conduction and haemodynamic compromise
• 6. Indwelling atrial-septal defect occluder device, or any anatomical reason that precludes left atrial access
• 7. Left atrial diameter (PLAX M-mode) >5.5 cm
• 8. Severe left ventricular dysfunction (LV ejection fraction < 30% on Echocardiography)
• 9. Recent stroke/transient ischaemic attack within 3 months
• 10. Inability or unwillingness to take oral anticoagulant treatment
• 11. Morbid obesity (Body Mass Index ≥40)
• 12. Extreme frailty (A score of 7,8 or worse on the Clinical Frailty Scale)
• 13. Implanted metal prosthetic valve(s) in mitral position
• 14. Indwelling cardiac resynchronisation therapy device, pacemaker or implantable cardioverter defibrillator
• 15. Advanced Renal dysfunction (eGFR<30 ml/min)
• 16. Pregnancy
• 17. Severe valvular heart disease of any kind as assessed by the investigator
• 18. Previous valve replacement surgery or other prosthetic heart valve

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiofrequency ablation of CTI; Radiofrequency ablation of CTI (cavo-tricuspid isthmus), which is the 'conventional' treatment of atrial flutter	Procedure: Radiofrequency ablation of CTI; Delivery of radiofrequency energy to the cavotricuspid isthmus (region of right atrial tissue between the tricuspid annulus and the inferior vena cava) until bidirectional block is achieved; Other Names: CTI ablation
Active Comparator: Cryoballoon PVI; Cryoballoon PVI (Pulmonary Vein Isolation), which is the 'novel treatment'	Procedure: Cryoballoon PVI; Cryoballoon application to the pulmonary veins aiming for Pulmonary Vein Isolation; Other Names: Cryoablation Pulmonary Vein Isolation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first recurrence of sustained, symptomatic supraventricular arrhythmia (Atrial Fibrillation, Atrial Flutter or Atrial Tachycardia) following a blanking period of 4 weeks after a single ablation procedure	'Sustained' is defined as lasting >30 seconds. 'Symptomatic' is defined as acute onset awareness of palpitations, breathlessness, dizziness, fatigue or chest pain associated with patient activation of the loop recorder.	After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first symptomatic or asymptomatic Atrial Fibrillation lasting ≥2 min	How long it takes until first occurrence of atrial fibrillation (associated with symptoms or no symptoms) lasting 2 or more minutes after blanking period. Two minutes is the minimum duration detectable by the loop recorder	After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
Total Burden of Atrial fibrillation over 12 months	The total occurrence of atrial fibrillation recorded by the loop recorder (symptomatic or asymptomatic) during the follow-up period	After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
Time to first symptomatic or asymptomatic atrial flutter/atrial tachycardia	Occurrence of atrial flutter/atrial tachycardia with/without symptoms following the blanking period	After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
Incidence of any significant arrhythmia	Incidence of any arrhythmia requiring medical visit to primary or secondary care, or hospitalisation, or leading to death	After first ablation procedure, through study completion, an average of 12 months
Total burden of abnormal heart rhythm measured by the implantable loop recorder	Total arrhythmic burden up to end of follow up or up to time of intervention (either cardioversion or ablation), whichever comes first.	After first ablation procedure through study completion or time of intervention, whichever comes first, assessed up to 12 months
Incidence of repeat electrophysiological interventional procedure (repeat catheter ablation, or DCCV) over the follow-up period.	Occurrence of repeat ablations/cardioversion	After 4 weeks of ablation treatment (blanking period) up to 12 months of follow up
Incidence of procedural complications	Composite of cardiac tamponade requiring drainage, persistent phrenic nerve palsy lasting >24 hours, serious vascular complications requiring intervention or delaying discharge, stroke/transient ischaemic attack, requirement for a permanent pacemaker, atrio-esophageal fistula, or death	During and after ablation procedure, through study completion, an average of 12 months
Incidence of all-cause hospitalisations	Any hospital admission post-ablation	After first ablation procedure, through study completion, an average of 12 months
Quality of Life questionnaire	Quality of life as assessed by the standard EuroQol Group's 5-dimensional questionnaire. This comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and the visual analogue scale. The single digits for the five dimensions will be combined into a 5-digit number that describes the patient's health state.	At baseline and at 12 months
Procedural duration	Duration of ablation measured in minutes for either treatment	Only during the first ablation procedure
Total Fluoroscopy times	The total time in minutes during which patient will be exposed to radiation under each of the two treatment techniques	Only during the first ablation procedure

Collaborators and Investigators

• Sponsor: Liverpool Heart and Chest Hospital NHS Foundation Trust
• Collaborators: Medtronic International Trading Sarl
• Investigators: Study Chair: Dhiraj Gupta, MBBS MD FRCP, Liverpool Heart and Chest Hospital

Publications and helpful links

General Publications

• Wazni O, Marrouche NF, Martin DO, Gillinov AM, Saliba W, Saad E, Klein A, Bhargava M, Bash D, Schweikert R, Erciyes D, Abdul-Karim A, Brachman J, Gunther J, Pisano E, Potenza D, Fanelli R, Natale A. Randomized study comparing combined pulmonary vein-left atrial junction disconnection and cavotricuspid isthmus ablation versus pulmonary vein-left atrial junction disconnection alone in patients presenting with typical atrial flutter and atrial fibrillation. Circulation. 2003 Nov 18;108(20):2479-83. doi: 10.1161/01.CIR.0000101684.88679.AB. Epub 2003 Nov 10.
• Schneider R, Lauschke J, Tischer T, Schneider C, Voss W, Moehlenkamp F, Glass A, Diedrich D, Bansch D. Pulmonary vein triggers play an important role in the initiation of atrial flutter: Initial results from the prospective randomized Atrial Fibrillation Ablation in Atrial Flutter (Triple A) trial. Heart Rhythm. 2015 May;12(5):865-71. doi: 10.1016/j.hrthm.2015.01.040. Epub 2015 Jan 28.
• De Bortoli A, Shi LB, Ohm OJ, Hoff PI, Schuster P, Solheim E, Chen J. Incidence and clinical predictors of subsequent atrial fibrillation requiring additional ablation after cavotricuspid isthmus ablation for typical atrial flutter. Scand Cardiovasc J. 2017 Jun;51(3):123-128. doi: 10.1080/14017431.2017.1304570. Epub 2017 Mar 23.
• Ding WY, Williams E, Das M, Tovmassian L, Tayebjee M, Haywood G, Martin C, Rajappan K, Bates M, Temple IP, Reichlin T, Chen Z, Balasubramaniam R, Ronayne C, Clarkson N, Mahida S, Sticherling C, Gupta D. Cryoballoon pulmonary vein isolation as first line treatment for typical atrial flutter (CRAFT): study protocol for a randomised controlled trial. J Interv Card Electrophysiol. 2021 Apr;60(3):427-432. doi: 10.1007/s10840-020-00746-6. Epub 2020 May 8.
• Gupta D, Ding WY, Calvert P, Williams E, Das M, Tovmassian L, Tayebjee MH, Haywood G, Martin CA, Rajappan K, Bates MGD, Temple IP, Reichlin T, Chen Z, Balasubramaniam RN, Ronayne C, Clarkson N, Morgan M, Barton J, Kemp I, Mahida S, Sticherling C. Cryoballoon Pulmonary Vein Isolation as First-Line Treatment for Typical Atrial Flutter. Heart. 2023 Feb 14;109(5):364-371. doi: 10.1136/heartjnl-2022-321729.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2018
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): November 1, 2023

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: January 9, 2018
• First Posted (Actual): January 17, 2018

Study Record Updates

• Last Update Posted (Actual): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Radiofrequency ablation; Cryoballoon ablation; Pulmonary Vein Isolation; Cavo-tricuspid isthmus
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Flutter
• Other Study ID Numbers: 1153

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

There is no plan to share Individual Participant Data with other researchers.

Supporting information that will be shared are only:

Study Protocol, Statistical Analysis Plan (SAP), and Clinical Study Report (CSR)

Data will be available after about 6 months for about 5 years.

Criteria for which Individual Participant Data and any additional supporting information will be shared, including with whom, for what types of analyses, and by what mechanism:

These will be shared with research co-workers, for results, statistical analysis and conclusions. Communication of anonymized data will be done via secure mails and emails.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No