Persistent Atrial FibrillationORBICA-AFNCT06096246
Investigation of Cardioversion Versus Therapeutic Ablation for Persistent AF (ORBICA-AF)
A study testing Pulmonary vein isolation, DC Cardioversion and Implantable loop recorder in people with Persistent Atrial Fibrillation and Cardiac Arrhythmia, run by Barts & The London NHS Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Persistent Atrial Fibrillation, Cardiac Arrhythmia, Catheter Ablation
- What is being tested?
- Pulmonary vein isolation, DC Cardioversion and Implantable loop recorder
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 208 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Jul 2024to 5 Dec 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Barts Heart Centre
London, EC1A 7BE
Malcolm Finlay, 02037658635, malcolm.finlay1@nhs.net
Vijayabharathy Kanthasamy, 02037658635, vijayabharathy.kanthasamy@nhs.net
About this study
Official title: Objective Randomised Blinded Investigation of Cardioversion Versus Ablation for Persistent Atrial Fibrillation (ORBICA-AF)
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.
Read the 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.
- Being tested
- Pulmonary vein isolation, DC Cardioversion, Implantable loop recorder, Femoral sheath insertion
- Medical subject headings
- Atrial Fibrillation, Arrhythmias, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulmonary vein isolationProcedure or surgery
Also called Catheter ablation
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 CardioversionProcedure or surgery
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 recorderDevice
Also called Reveal LINQ
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 insertionProcedure or surgery
Two femoral sheaths (7Fr) will be inserted using ultrasound guidance under local anaesthetic.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: DCCV + PVI | Active comparator | 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). Receives: Procedure: Pulmonary vein isolation; Procedure: DC Cardioversion; Device: Implantable loop recorder; Procedure: Femoral sheath insertion |
| DC cardioversion (DCCV) + Sham procedure | Sham comparator | 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. Receives: Procedure: DC Cardioversion; Device: Implantable loop recorder; Procedure: Femoral sheath insertion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]
Measured: Within 12 months following the procedure
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
Measured: 3 months post randomisation
Secondary outcomes (15)
Death
Death of the patient
Measured: Within 12 months of study index procedure.
Rates of Subject Hospital re-admission
Rates of admission of the subject back to hospital following the initial treatment for AF
Measured: Within 12 months of study index procedure.
Procedural complications
Assessment of rates of events that are considered procedural complications during the DCCV +/- Pulmonary Vein isolation (PVI) procedure
Measured: Up to 7 days post procedure
Bleeding events
Rates of bleeding in subjects following the study DCCV +/- pulmonary vein isolation (PVI) procedures
Measured: Within 7 days of the index procedure
Rates of Repeat procedures
Requirement for repeat procedures following the initial DCCV +/- pulmonary vein isolation (PVI) procedure for the study
Measured: within 12 months following the procedure
Cardiac function
Measurement of change in ejection fraction by echocardiogram
Measured: between baseline and 12 months following the procedure
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.
Measured: Within 12 months following the index procedure
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.
Measured: Between baseline and 3, 6 and 12 months after procedure
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
Measured: Between baseline and 3, 6 and 12 months after procedure
Measuring Blinding index
Assessing the maintenance of blinding measured by Blinding index in both study participant and blinded medical staff.
Measured: Day 0 (within 24 hours post randomisation) and 3 months
Measuring AF Burden
Percentage time the patient is in AF as measured by the ILR (Implantable loop recorder) device compared to pre-randomisation
Measured: At 3, 6 and 12 months follow up
The occurrence of atrial tachyarrhythmias
Assessment of the occurence of other atrial tachyarrhythmia (Atrial flutter or Atrial tachycardia) in the continuous monitoring
Measured: Within 12 months following the index procedure
Symptomatic Atrial fibrillation/Atrial tachycardia episodes
Number of symptomatic AF/AT triggered/reported by patients correlating to true episodes in the continuous monitoring.
Measured: At 3, 6, 12 months follow up
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
Measured: Between baseline and 12months after procedure
Composite adverse events
Assessment of rates of adverse events during follow up
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2023
- Study start26 Jul 2024
- Primary completion26 Jul 2027 (estimated)
- Study completion5 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Persistent Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised, blinded, controlled trial with 2 arms
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 208 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Barts & The London NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard Schilling, FRCP MD, Study chair, Barts & The London NHS TrustMalcolm Finlay, Principal investigator, Barts & The London NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06096246
- Sponsor's protocol ID
- ORBICA-AF
- Acronym
- ORBICA-AF
- Status last verified
- Sep 2026
- First submitted
- 21 Sep 2023
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 24850821Redberg 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.
PubMed 25184861Miller 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.
PubMed 15574854Jones 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.
PubMed 24948694Brim 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.
PubMed 23239742Al-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.
PubMed 29103656Bang 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.
PubMed 15020033