Clinical trial NCT06096246: Investigation of Cardioversion Versus Therapeutic Ablation for Persistent AF (ORBICA-AF)
Official title: Objective Randomised Blinded Investigation of Cardioversion Versus Ablation for Persistent Atrial Fibrillation (ORBICA-AF)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Persistent Atrial Fibrillation
Cardiac Arrhythmia
Catheter Ablation
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
First posted: 2023-10-23
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, blinded, controlled trial with 2 arms
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Recurrence of Persistent AF (AF episode lasting > 7 days) or left atrial ablation/ DC Cardioversion for atrial arrhythmia after 6 weeks of blanking period.
timeFrame: Within 12 months following the procedure
measure: A change in the burden of AF, as measured by continuous monitoring through ILR (Implantable loop recorder) at 3 months
timeFrame: 3 months post randomisation
Secondary outcomes:
measure: Death
timeFrame: Within 12 months of study index procedure.
measure: Rates of Subject Hospital re-admission
timeFrame: Within 12 months of study index procedure.
measure: Procedural complications
timeFrame: Up to 7 days post procedure
measure: Bleeding events
timeFrame: Within 7 days of the index procedure
measure: Rates of Repeat procedures
timeFrame: within 12 months following the procedure
measure: Cardiac function
timeFrame: between baseline and 12 months following the procedure
measure: Percentage of clinical success of procedure
timeFrame: Within 12 months following the index procedure
measure: Change in quality of life score using in 12 item Short Form health survey (SF12)
timeFrame: Between baseline and 3, 6 and 12 months after procedure
measure: Change in quality of life measures using Atrial Fibrillation Effect on QualiTy-of-life(AFEQT) questionnaire
timeFrame: Between baseline and 3, 6 and 12 months after procedure
measure: Measuring Blinding index
timeFrame: Day 0 (within 24 hours post randomisation) and 3 months
measure: Measuring AF Burden
timeFrame: At 3, 6 and 12 months follow up
measure: The occurrence of atrial tachyarrhythmias
timeFrame: Within 12 months following the index procedure
measure: Symptomatic Atrial fibrillation/Atrial tachycardia episodes
timeFrame: At 3, 6, 12 months follow up
measure: Antiarrhythmic drug use
timeFrame: Between baseline and 12months after procedure
measure: Composite adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts Heart Centre
Study officials:
affiliation: Barts & The London NHS Trust
name: Richard Schilling, FRCP MD
role: STUDY_CHAIR
affiliation: Barts & The London NHS Trust
name: Malcolm Finlay
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
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