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

Persistent Atrial Fibrillation Clinical Trial

— ORBICA-AF  

Official title:

Objective Randomised Blinded Investigation of Cardioversion Versus Ablation for Persistent Atrial Fibrillation (ORBICA-AF)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06096246
• Other study ID #: ORBICA-AF
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 5, 2024
• Est. completion date: December 5, 2027

Study information

• Verified date: April 2024
• Source: Barts & The London NHS Trust
• Contact: Malcolm Finlay, FRCP PhD
• Phone: 02037658635
• Email: malcolm.finlay1[@]nhs.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 208
• Est. completion date: December 5, 2027
• Est. primary completion date: August 5, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Atrial Fibrillation
• Cardiac Arrhythmia
• Catheter Ablation
• Persistent Atrial Fibrillation

Intervention

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.
• 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 .

Procedure:
• Femoral sheath insertion
Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Barts & The London NHS Trust

References & Publications (7)

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 S — View Citation

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. — View 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. — View 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. Erratum In: BMJ. 2014;349:g4440. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of Persistent AF (AF episode lasting > 7 days) or left atrial ablation/ DC Cardioversion for atrial arrhythmia after 6 weeks of blanking period.	Rates of recurrence of arrhythmia and 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]	Within 12 months following the procedure
Primary	A change in the burden of AF, as measured by continuous monitoring through ILR (Implantable loop recorder) at 3 months	Percentage time the patient is in AF as measured by the ILR device (in percentage) compared to pre-randomisation	3 months post randomisation
Secondary	Death	Death of the patient	Within 12 months of study index procedure.
Secondary	Rates of Subject Hospital re-admission	Rates of admission of the subject back to hospital following the initial treatment for AF	Within 12 months of study index procedure.
Secondary	Procedural complications	Assessment of rates of events that are considered procedural complications during the DCCV +/- Pulmonary Vein isolation (PVI) procedure	Up to 7 days post procedure
Secondary	Bleeding events	Rates of bleeding in subjects following the study DCCV +/- pulmonary vein isolation (PVI) procedures	Within 7 days of the index procedure
Secondary	Rates of Repeat procedures	Requirement for repeat procedures following the initial DCCV +/- pulmonary vein isolation (PVI) procedure for the study	within 12 months following the procedure
Secondary	Cardiac function	Measurement of change in ejection fraction by echocardiogram	between baseline and 12 months following the procedure
Secondary	Percentage of clinical success of 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.	Within 12 months following the index procedure
Secondary	Change in quality of life score using in 12 item Short Form health survey (SF12)	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.	Between baseline and 3, 6 and 12 months after procedure
Secondary	Change in quality of life measures using Atrial Fibrillation Effect on QualiTy-of-life(AFEQT) questionnaire	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	Between baseline and 3, 6 and 12 months after procedure
Secondary	Measuring Blinding index	Assessing the maintenance of blinding measured by Blinding index in both study participant and blinded medical staff.	Day 0 (within 24 hours post randomisation) and 3 months
Secondary	Measuring AF Burden	Percentage time the patient is in AF as measured by the ILR (Implantable loop recorder) device compared to pre-randomisation	At 3, 6 and 12 months follow up
Secondary	The occurrence of atrial tachyarrhythmias	Assessment of the occurence of other atrial tachyarrhythmia (Atrial flutter or Atrial tachycardia) in the continuous monitoring	Within 12 months following the index procedure
Secondary	Symptomatic Atrial fibrillation/Atrial tachycardia episodes	Number of symptomatic AF/AT triggered/reported by patients correlating to true episodes in the continuous monitoring.	At 3, 6, 12 months follow up
Secondary	Antiarrhythmic drug use	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	Between baseline and 12months after procedure
Secondary	Composite adverse events	Assessment of rates of adverse events during follow up	12 months