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

NCT ID: NCT06096246

Last Updated: 2025-09-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-26
• Study Completion Date: 2027-12-05

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.

Conditions

Persistent Atrial Fibrillation; Cardiac Arrhythmia; Catheter Ablation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Pulmonary vein isolation

Intervention Type: PROCEDURE

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.

DC Cardioversion

Intervention Type: PROCEDURE

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.

Implantable loop recorder

Intervention Type: DEVICE

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 .

Femoral sheath insertion

Intervention Type: PROCEDURE

Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.

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.

Group Type: SHAM_COMPARATOR

DC Cardioversion

Intervention Type: PROCEDURE

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.

Implantable loop recorder

Intervention Type: DEVICE

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 .

Femoral sheath insertion

Intervention Type: PROCEDURE

Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

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 .

Intervention Type: DEVICE

Femoral sheath insertion

Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.

Intervention Type: PROCEDURE

Other Intervention Names

Catheter ablation; Reveal LINQ

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Barts & The London NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Schilling, FRCP MD

Role: STUDY_CHAIR

Barts & The London NHS Trust

Malcolm Finlay

Role: PRINCIPAL_INVESTIGATOR

Barts & The London NHS Trust

Locations

Barts Heart Centre

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Malcolm Finlay, FRCP PhD

Role: CONTACT

malcolm.finlay1@nhs.net

02037658635

Vijayabharathy Kanthasamy, MRCP

Role: CONTACT

vijayabharathy.kanthasamy@nhs.net

02037658635

Facility Contacts

Malcolm Finlay

Role: primary

malcolm.finlay1@nhs.net

02037658635

Vijayabharathy Kanthasamy

Role: backup

vijayabharathy.kanthasamy@nhs.net

02037658635

References

Wartolowska K, Judge A, Hopewell S, Collins GS, Dean BJ, Rombach I, Brindley D, Savulescu J, Beard DJ, Carr AJ. Use of placebo controls in the evaluation of surgery: systematic review. BMJ. 2014 May 21;348:g3253. doi: 10.1136/bmj.g3253.

Reference Type: RESULT

PMID: 24850821 (View on PubMed)

Redberg RF. Sham controls in medical device trials. N Engl J Med. 2014 Sep 4;371(10):892-3. doi: 10.1056/NEJMp1406388. No abstract available.

Reference Type: RESULT

PMID: 25184861 (View on PubMed)

Miller FG, Kaptchuk TJ. Sham procedures and the ethics of clinical trials. J R Soc Med. 2004 Dec;97(12):576-8. doi: 10.1177/014107680409701205. No abstract available.

Reference Type: RESULT

PMID: 15574854 (View on PubMed)

Jones C, Pollit V, Fitzmaurice D, Cowan C; Guideline Development Group. The management of atrial fibrillation: summary of updated NICE guidance. BMJ. 2014 Jun 19;348:g3655. doi: 10.1136/bmj.g3655. No abstract available.

Reference Type: RESULT

PMID: 24948694 (View on PubMed)

Brim RL, Miller FG. The potential benefit of the placebo effect in sham-controlled trials: implications for risk-benefit assessments and informed consent. J Med Ethics. 2013 Nov;39(11):703-7. doi: 10.1136/medethics-2012-101045. Epub 2012 Dec 13.

Reference Type: RESULT

PMID: 23239742 (View on PubMed)

Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS, Petraco R, Cook C, Ahmad Y, Howard J, Baker C, Sharp A, Gerber R, Talwar S, Assomull R, Mayet J, Wensel R, Collier D, Shun-Shin M, Thom SA, Davies JE, Francis DP; ORBITA investigators. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. Lancet. 2018 Jan 6;391(10115):31-40. doi: 10.1016/S0140-6736(17)32714-9. Epub 2017 Nov 2.

Reference Type: RESULT

PMID: 29103656 (View on PubMed)

Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004 Apr;25(2):143-56. doi: 10.1016/j.cct.2003.10.016.

Reference Type: RESULT

PMID: 15020033 (View on PubMed)

Other Identifiers

ORBICA-AF

Identifier Type: -

Identifier Source: org_study_id