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Investigation of Therapeutic Ablation Versus Cardioversion for AF

Not Applicable
Completed
Conditions
Persistent Atrial Fibrillation
Cardiac Arrhythmia
Interventions
Procedure: DC Cardioversion
Procedure: Pulmonary vein isolation
Device: Implantable loop recorder
Registration Number
NCT03907982
Lead Sponsor
Barts & The London NHS Trust
Brief Summary

The main aim of the research is to investigate whether patients undergoing pulmonary vein isolation with cryoablation for atrial fibrillation (AF) will have lower rates of AF recurrence than those treated by DC cardioversion without an ablation procedure. The objectives of the Pilot Study are to validate the key study logistics with a view to optimising methods to be used in the main study.

Detailed Description

After adequate stroke prevention (e.g. anticoagulation) and rate control, the optimum strategy for patients who continue to be symptomatic with persistent AF has not been established. Cardioversion with antiarrhythmic medication is commonly used as a first-line rhythm control strategy despite very high recurrence rates of the index arrhythmia and high serious complications associated with this strategy. Further treatment options, such as catheter ablation or implantation of a pacemaker and ablation of the atrioventricular (AV) node, are considered once AF recurs. The benefits of first-line ablation in patients presenting with persistent AF has not been tested. We seek to perform a blinded, randomised trial comparing an electrical cardioversion-led strategy with a pulmonary-vein isolation strategy for the treatment of persistent atrial fibrillation.

No blinded randomised controlled trial comparing early-ablation strategies to cardioversion-led strategies has been performed. The rationale for blinding where possible in clinical trials is well established. The recently published ORBITA trial performed a blinded, multicentre randomised trial of percutaneous coronary intervention (PCI) in stable angina compared to a placebo procedure. This trial demonstrated that the efficacy of invasive procedures can be assessed with a placebo procedure and that this type of trial remains necessary. Knowledge of treatment assignment influences physician behaviour, drug recommendations and encourages bias in outcome reporting. The treatment effect size and the effects of confounding factors will be exaggerated and thus limit the interpretation of the true patient experienced outcomes either strategy. In a comparison of surgical procedures, a sham-control arm represents the gold standard of blinding. A systematic review of placebo-controlled surgical trials found no evidence of harm to participants assigned to the placebo group. For a procedure whose primary purpose is to give sustained symptomatic relief, definitive quantification of the true placebo-controlled effect size of AF ablation is necessary. There is a need to clarify the relationship between patient reported symptoms and the arrhythmia itself. Patient reported symptoms may not always be related to the severity of the arrhythmia or quality of life. No bias-resistant blinded, randomised, trial has yet been performed seeking to measure the benefits of AF ablation.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria

Patients who meet the following inclusion criteria will be eligible for the study;

  • Ability to give informed consent
  • Age 18-80 years
  • Persistent AF (atrial fibrillation lasting > 7days) of total continuous duration <2 years as documented in medical notes.
  • Patients being considered for cardioversion.
Exclusion Criteria

Patients who meet the following exclusion criteria will be ineligible for study participation;

  • Creatinine clearance (eGFR) < 30mls/min
  • Contraindication or unable to take anticoagulation
  • Known contraindication to or unable to tolerate amiodarone
  • Uncontrolled hypertension
  • Contraindication to catheter ablation
  • BMI > 35

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DCCV + PVIPulmonary vein isolationDC cardioversion (DCCV) plus Pulmonary Vein Isolation (Cryoablation) At end of pulmonary vein isolation, DCCV performed (if patient still in AF). An implantable loop recorder will be inserted in the prepectoral area with local anaesthetic at the end of the procedure.
DC cardioversion (DCCV)DC CardioversionAcute treatment of heart rhythm by cardioversion. An implantable loop recorder will be inserted in the prepectoral area with local anaesthetic at the end of the procedure.
DCCV + PVIDC CardioversionDC cardioversion (DCCV) plus Pulmonary Vein Isolation (Cryoablation) At end of pulmonary vein isolation, DCCV performed (if patient still in AF). An implantable loop recorder will be inserted in the prepectoral area with local anaesthetic at the end of the procedure.
DC cardioversion (DCCV)Implantable loop recorderAcute treatment of heart rhythm by cardioversion. An implantable loop recorder will be inserted in the prepectoral area with local anaesthetic at the end of the procedure.
DCCV + PVIImplantable loop recorderDC cardioversion (DCCV) plus Pulmonary Vein Isolation (Cryoablation) At end of pulmonary vein isolation, DCCV performed (if patient still in AF). An implantable loop recorder will be inserted in the prepectoral area with local anaesthetic at the end of the procedure.
Primary Outcome Measures
NameTimeMethod
Recurrence of Persistent AF (AF episode lasting > 7 days).Within 12 months following the procedure

Data on epsiodes of Atrial Fibrillation (rate, duration) will be provided by the loop recorder, and downloaded via a home monitoring system

Secondary Outcome Measures
NameTimeMethod
DeathWithin 12 months of study recruitment

Death of the patient

Procedural complicationsAt the time of the procedure

Assessment of rates of events that are considered procedural complications during the DCCV +/- Pulmonary Vein isolation (PVI) procedure

Bleeding eventsWithin 7 days of the procedure

Rates of bleeding in subjects following the study DCCV +/- pulmonary vein isolation (PVI) procedures

Clinical success of procedureWithin 12 months following the procedure

Clinical procedural success as defined by 75% or greater reduction in the number of AF episodes as measured by the insertable cardiac monitoring system (LINQ) device.

Rates of Repeat procedureswithin 12 months following the procedure

Requirement for repeat procedures following the initial DCCV +/- pulmonary vein isolation (PVI) procedure for the study

Change in quality of life measures (SF12)Between baseline and 12 months after procedure

Assessment of quality of life measures using Short Form Health Survey (SF12) questionnaire, which is a multipurpose short form survey with 12 questions, all selected from the SF-36 Health Survey (Ware, Kosinski, and Keller, 1996). The questions are combined, scored, and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. Higher scores indicate a better outcome.

Rates of Subject Hospital re-admissionWithin 12 months following the procedure

Rates of admission of the subject back to hospital following the initial treatment for AF

Cardiac functionbetween baseline and 12 months following the procedure

Measurement of change in ejection fraction by echocardiogram

Change in quality of life measures (AF-PROMS)between baseline and 12 months after procedure

Assessment of patient reported outcome measures (PROMS) specific for atrial fibrillation (AF) in a series of 28 questions to assess the impact of AF on the subject's quality of life. Higher scores indicate a better outcome.

Antiarrhythmic drug useBetween baseline and 12months after procedure

Assessment of the use of antiarrhythmic drugs (combined data collected on duration , dose and frequency of drug use) prior to and after the DCCV +/- PVI procedure

Trial Locations

Locations (1)

Barts Health NHS Trust - St Bartholomew's Hospital and Whipps Cross Hospital

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London, United Kingdom

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