Investigation of Cardioversion Versus Therapeutic Ablation for Persistent AF (ORBICA-AF)
- Conditions
- Persistent Atrial FibrillationCardiac ArrhythmiaCatheter Ablation
- Interventions
- Procedure: Pulmonary vein isolationProcedure: DC CardioversionDevice: Implantable loop recorderProcedure: Femoral sheath insertion
- Registration Number
- NCT06096246
- 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 catheter ablation for persistent atrial fibrillation (AF) will have lower rates of AF recurrence than those treated by DC cardioversion without an ablation procedure.
- 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 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 have not been tested. Investigators 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 of 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 in persistent AF. The investigators of this trial have achieved successful recruitment and concluded the pilot phase (ORBITA AF trial; ClinicalTrials.gov Identifier: NCT03907982) with the goal of assessing feasibility and optimizing the study protocol prior to conducting a larger trial. The positive outcomes of the pilot phase have paved the way for this larger follow-on trial.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 208
- Ability to give informed consent
- Age 18-85 years
- Persistent AF (atrial fibrillation lasting > 7days) of total continuous duration <2 years as documented in medical notes.
- Patients being considered for cardioversion.
- Creatinine clearance (eGFR) < 30mls/min
- Contraindication or unable to take anticoagulation
- Uncontrolled hypertension
- Contraindication for catheter ablation
- BMI > 40
- Patients in Persistent AF who have had more than one previous cardioversion.
- Established diagnosis of Hypertrophic cardiomyopathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental: DCCV + PVI Pulmonary vein isolation An implantable loop recorder will be inserted in the pre pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for ablation and for phrenic nerve pacing during the procedure. DC cardioversion (DCCV) plus Pulmonary Vein Isolation - At the end of pulmonary vein isolation, DCCV is performed (if the patient is still in AF). Experimental: DCCV + PVI Implantable loop recorder An implantable loop recorder will be inserted in the pre pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for ablation and for phrenic nerve pacing during the procedure. DC cardioversion (DCCV) plus Pulmonary Vein Isolation - At the end of pulmonary vein isolation, DCCV is performed (if the patient is still in AF). Experimental: DCCV + PVI DC Cardioversion An implantable loop recorder will be inserted in the pre pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for ablation and for phrenic nerve pacing during the procedure. DC cardioversion (DCCV) plus Pulmonary Vein Isolation - At the end of pulmonary vein isolation, DCCV is performed (if the patient is still in AF). DC cardioversion (DCCV) + Sham procedure Femoral sheath insertion An implantable loop recorder will be inserted in the pre-pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for intermittent phrenic nerve pacing during the procedure. DC Cardioversion and Sham procedure will be performed after randomisation. Intermittent phrenic nerve pacing will be employed for the sham group through the femoral venous sheath using a quadripolar catheter. Experimental: DCCV + PVI Femoral sheath insertion An implantable loop recorder will be inserted in the pre pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for ablation and for phrenic nerve pacing during the procedure. DC cardioversion (DCCV) plus Pulmonary Vein Isolation - At the end of pulmonary vein isolation, DCCV is performed (if the patient is still in AF). DC cardioversion (DCCV) + Sham procedure DC Cardioversion An implantable loop recorder will be inserted in the pre-pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for intermittent phrenic nerve pacing during the procedure. DC Cardioversion and Sham procedure will be performed after randomisation. Intermittent phrenic nerve pacing will be employed for the sham group through the femoral venous sheath using a quadripolar catheter. DC cardioversion (DCCV) + Sham procedure Implantable loop recorder An implantable loop recorder will be inserted in the pre-pectoral area with local anaesthetic at least one week before the randomisation. Two femoral sheaths will be inserted at the groin area in all patients on the day of the procedure prior randomisation. This will be utilised as the access route for cardiac catheter insertion for intermittent phrenic nerve pacing during the procedure. DC Cardioversion and Sham procedure will be performed after randomisation. Intermittent phrenic nerve pacing will be employed for the sham group through the femoral venous sheath using a quadripolar catheter.
- Primary Outcome Measures
Name Time Method Recurrence of Persistent AF (AF episode lasting > 7 days) or left atrial ablation/ DC Cardioversion for atrial arrhythmia after 6 weeks of blanking period. Within 12 months following the procedure Rates of recurrence of arrhythmia and data on episodes of Atrial Fibrillation (rate, duration) will be provided by the loop recorder, and downloaded via a home monitoring system \[ rhythm on ILR ECG\]
A change in the burden of AF, as measured by continuous monitoring through ILR (Implantable loop recorder) at 3 months 3 months post randomisation Percentage time the patient is in AF as measured by the ILR device (in percentage) compared to pre-randomisation
- Secondary Outcome Measures
Name Time Method Bleeding events Within 7 days of the index procedure Rates of bleeding in subjects following the study DCCV +/- pulmonary vein isolation (PVI) procedures
Cardiac function between baseline and 12 months following the procedure Measurement of change in ejection fraction by echocardiogram
Change in quality of life measures using Atrial Fibrillation Effect on QualiTy-of-life(AFEQT) questionnaire Between baseline and 3, 6 and 12 months after procedure Assessment of AF specific symptoms to assess the impact of AF on the subject's quality of life. The responses on the 20-item AFEQT are scored on a 1 to 7 Likert scale. Overall and subscale scores range from 0 to 100. A score of 0 corresponds to complete disability, while a score of 100 describes the highest level of QoL
The occurrence of atrial tachyarrhythmias Within 12 months following the index procedure Assessment of the occurence of other atrial tachyarrhythmia (Atrial flutter or Atrial tachycardia) in the continuous monitoring
Composite adverse events 12 months Assessment of rates of adverse events during follow up
Rates of Subject Hospital re-admission Within 12 months of study index procedure. Rates of admission of the subject back to hospital following the initial treatment for AF
Antiarrhythmic drug use Between 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
Death Within 12 months of study index procedure. Death of the patient
Procedural complications Up to 7 days post procedure Assessment of rates of events that are considered procedural complications during the DCCV +/- Pulmonary Vein isolation (PVI) procedure
Percentage of clinical success of procedure Within 12 months following the index 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.
Change in quality of life score using in 12 item Short Form health survey (SF12) Between baseline and 3, 6 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. 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. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.
Measuring AF Burden At 3, 6 and 12 months follow up Percentage time the patient is in AF as measured by the ILR (Implantable loop recorder) device compared to pre-randomisation
Rates of Repeat procedures within 12 months following the procedure Requirement for repeat procedures following the initial DCCV +/- pulmonary vein isolation (PVI) procedure for the study
Symptomatic Atrial fibrillation/Atrial tachycardia episodes At 3, 6, 12 months follow up Number of symptomatic AF/AT triggered/reported by patients correlating to true episodes in the continuous monitoring.
Measuring Blinding index Day 0 (within 24 hours post randomisation) and 3 months Assessing the maintenance of blinding measured by Blinding index in both study participant and blinded medical staff.
Trial Locations
- Locations (1)
Barts Heart Centre
🇬🇧London, United Kingdom