Investigation of Cardioversion Versus Therapeutic Ablation for Persistent AF (ORBICA-AF)

Barts & The London NHS Trust

Status: Enrolling

Conditions: Persistent Atrial Fibrillation; Cardiac Arrhythmia; Catheter Ablation

Treatments: Device: Implantable loop recorder; Procedure: DC Cardioversion; Procedure: Femoral sheath insertion; Procedure: Pulmonary vein isolation

Study type: Interventional

Funder types: Other

Identifiers

NCT06096246

ORBICA-AF

Details and patient eligibility

About

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.

Full 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.

Enrollment: 208 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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208 participants in 2 patient groups

Experimental: DCCV + PVI

Active Comparator group

Description:

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).

Treatment:

Procedure: Pulmonary vein isolation

Procedure: Femoral sheath insertion

Procedure: DC Cardioversion

Device: Implantable loop recorder

DC cardioversion (DCCV) + Sham procedure

Sham Comparator group

Description:

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.

Treatment:

Procedure: Femoral sheath insertion

Procedure: DC Cardioversion

Device: Implantable loop recorder