Clinical trial NCT03907982: Investigation of Therapeutic Ablation Versus Cardioversion for AF
Official title: Objective Randomised Blinded Investigation of Therapeutic Ablation Versus Cardioversion for Persistent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Persistent Atrial Fibrillation
Cardiac Arrhythmia
Keywords: Cardiac ablation
Cardioversion
pacemaker
implantable cardioverter-defibrillator
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2019-04-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Internal Pilot as part of a future study, 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 cryoablation for atrial fibrillation (AF) will have lower rates of AF recurrence than those treated by DC cardioversion without an ablation procedure. The objectives of the Pilot Study are to validate the key study logistics with a view to optimising methods to be used in the main study.

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 the 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 has not been tested. We 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 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.

Eligibility criteria: Inclusion Criteria: Patients who meet the following inclusion criteria will be eligible for the study;

* Ability to give informed consent
* Age 18-80 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: Patients who meet the following exclusion criteria will be ineligible for study participation;

* Creatinine clearance (eGFR) \< 30mls/min
* Contraindication or unable to take anticoagulation
* Known contraindication to or unable to tolerate amiodarone
* Uncontrolled hypertension
* Contraindication to catheter ablation
* BMI \> 35

Primary outcomes:
measure: Recurrence of Persistent AF (AF episode lasting > 7 days).
timeFrame: Within 12 months following the procedure
Secondary outcomes:
measure: Death
timeFrame: Within 12 months of study recruitment
measure: Rates of Subject Hospital re-admission
timeFrame: Within 12 months following the procedure
measure: Procedural complications
timeFrame: At the time of the procedure
measure: Bleeding events
timeFrame: Within 7 days of the 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: Clinical success of procedure
timeFrame: Within 12 months following the procedure
measure: Change in quality of life measures (SF12)
timeFrame: Between baseline and 12 months after procedure
measure: Change in quality of life measures (AF-PROMS)
timeFrame: between baseline and 12 months after procedure
measure: Antiarrhythmic drug use
timeFrame: Between baseline and 12months after procedure
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts Health NHS Trust - St Bartholomew's Hospital and Whipps Cross Hospital
Study officials:
affiliation: Barts & The London NHS Trust
name: Richard Schilling, FRCP MD
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.
citation: 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.
citation: 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.
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.