Investigation of Therapeutic Ablation Versus Cardioversion for AF
Condition: Persistent Atrial Fibrillation; Cardiac Arrhythmia
MeSH terms: Atrial Fibrillation; Arrhythmias, Cardiac
Study type: Interventional

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.
    

Intervention name(s): DC Cardioversion; Pulmonary vein isolation; Implantable loop recorder
Intervention type(s): Procedure; Procedure; Device
Intervention description(s): DC cardioversion (DCCV) is used to treat irregular heart rhythms (commonly atrial fibrillation). The procedure involves sedation or anaesthetic and placement of electrodes on the chest. An electrical impulse is passed across the electrodes to return the heart rhythm to normal.; The cryoballoon (CE marked) is the key specified technique for performing pulmonary vein isolation in the ablation arm in this trial. This allows the physician electrophysiologist to perform a circumferential freeze around the pulmonary veins to electrically isolate the vein, thus preventing pulmonary vein ectopy from triggering AF.; The Reveal device is inserted in the pre-pectoral position under the skin. This is performed with local anaesthetic and sedation at the end of the procedure clinic by the electrophysiologist performing the procedure. The device will provide a continuous recording of the heart rhythm and rate, and will be able to down load duration of AF episodes via a home monitoring system to establish the primary endpoint of the study.
Other intervention name(s): LINQ
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Internal Pilot as part of a future study, Randomised, blinded, controlled trial with 2 arms.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Cardiac ablation; Cardioversion; pacemaker; implantable cardioverter-defibrillator