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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Recurrence of Persistent AF (AF episode lasting > 7 days) or left atrial ablation/ DC Cardioversion for atrial arrhythmia after 6 weeks of blanking period. [Срок оценки: 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 [Срок оценки: 3 months post randomisation]

Вторичные конечные точки (12)

• Death [Срок оценки: Within 12 months of study index procedure.]
• Rates of Subject Hospital re-admission [Срок оценки: Within 12 months of study index procedure.]
• Procedural complications [Срок оценки: Up to 7 days post procedure]
• Bleeding events [Срок оценки: Within 7 days of the index procedure]
• Rates of Repeat procedures [Срок оценки: within 12 months following the procedure]
• Cardiac function [Срок оценки: between baseline and 12 months following the procedure]
• Percentage of clinical success of procedure [Срок оценки: Within 12 months following the index procedure]
• Change in quality of life score using in 12 item Short Form health survey (SF12) [Срок оценки: 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 [Срок оценки: Between baseline and 3, 6 and 12 months after procedure]
• Measuring Blinding index [Срок оценки: Day 0 (within 24 hours post randomisation) and 3 months]
• Measuring AF Burden [Срок оценки: At 3, 6 and 12 months follow up]
• The occurrence of atrial tachyarrhythmias [Срок оценки: Within 12 months following the index procedure]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Великобритания · 1 центр

• Barts Heart Centre — London

Публикации

• 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. PMID 24850821
• 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. PMID 25184861
• 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. PMID 15574854
• 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. PMID 24948694
• 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. PMID 23239742
• 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 controll PMID 29103656
• 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. PMID 15020033

Идентификаторы

NCT: NCT06096246 · ORBICA-AF

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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