Investigation of Cardioversion Versus Therapeutic Ablation for Persistent AF (ORBICA-AF)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Experimental: DCCV + PVI 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). |
Procedure: Pulmonary vein isolation
The catheter ablation (with a CE [Conformité Européenne] marked device) 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 ablation around the pulmonary veins to electrically isolate the vein, thus preventing pulmonary vein ectopy from triggering AF.
Other Names:
Procedure: DC Cardioversion
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.
Device: Implantable loop recorder
The Reveal device is inserted in the pre-pectoral position under the skin. This is performed with local anaesthetic and sedation at least a week before the randomisation. The device will provide a continuous recording of the heart rhythm and rate, and will be able to download duration of AF episodes via a home monitoring system to establish the primary endpoint of the study .
Other Names:
Procedure: Femoral sheath insertion
Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.
|
| Sham Comparator: DC cardioversion (DCCV) + Sham procedure 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. |
Procedure: DC Cardioversion
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.
Device: Implantable loop recorder
The Reveal device is inserted in the pre-pectoral position under the skin. This is performed with local anaesthetic and sedation at least a week before the randomisation. The device will provide a continuous recording of the heart rhythm and rate, and will be able to download duration of AF episodes via a home monitoring system to establish the primary endpoint of the study .
Other Names:
Procedure: Femoral sheath insertion
Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.
|
Outcome Measures
Primary Outcome Measures
- Recurrence of Persistent AF (AF episode lasting > 7 days) and other persistent atrial arrhythmias after 6 weeks of blanking period [Within 12 months following the procedure]
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]
- Recurrence of other persistent atrial arrhythmias after 6 weeks of blanking period. [Within 12 months following the procedure]
Data on episodes of atrial arrhythmia other than AF 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
- Repeat procedure for treatment of Paroxysmal AF [within 12 months following the procedure]
Number of participants requiring repeat procedure for paroxysmal AF following the initial DCCV +/- pulmonary vein isolation (PVI) procedure for the study
Secondary Outcome Measures
- Death [Within 12 months of study index procedure.]
Death of the patient
- 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
- 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
- Bleeding events [Within 7 days of the index procedure]
Rates of bleeding in subjects following the study DCCV +/- pulmonary vein isolation (PVI) procedures
- 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
- Cardiac function [between baseline and 12 months following the procedure]
Measurement of change in ejection fraction by echocardiogram
- 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.
- 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
- 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.
- 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
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Barts & The London NHS Trust
Investigators
- Study Chair: Richard Schilling, FRCP MD, Barts & The London NHS Trust
- Principal Investigator: Malcolm Finlay, Barts & The London NHS Trust
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ORBICA-AF