First-line Cryoablation for Early Treatment of Persistent Atrial Fibrillation - a Randomized Study Comparing Early Trigger Isolation Using the Cryoballoon Versus Antiarrhythmic Medication
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 试验地点
- 6
- 主要终点
- Proportion of patients free from first atrial tachyarrhythmia recurrence lasting 6 minutes or longer
研究概览
简要总结
The goal of this multicentre, prospective, randomized, open, blinded for evaluation of end point (PROBE) controlled parallel-group superiority trial, is to compare the efficacy of antiarrhythmic drug (AAD) therapy and cryoballoon pulmonary vein isolation (PVI) regarding freedom from atrial fibrillation (%) assessed by an implantable cardiac monitor (ICM), ECG tracing or Holter at 12 months in patients with persistent AF. The main question[s] it aims to answer are:
-
Will first-line cryoballoon ablation for PVI compared to AAD, result in 25 % higher freedom from atrial tachyarrhythmias lasting > 6 minutes at 12 months (primary outcome) excluding three months initial blanking period, in patients with symptomatic and recurrent persistent AF?
-
Will first-line cryoablation for PVI, compared to AAD result in a superior improvement in health related Quality of Life (HRQoL), AF/AT burden, AF/AT progression and reversion, more reverse atrial remodeling, cognitive function, healthcare utilization with associated costs, better safety, at 12-24-36 months as compared with drug use? Participants will be randomized 1:1 to first-line PVI using the cryoballoon or to first-line antiarrhythmic drug therapy and during 3 years follow-up undergo regular;
-
Continuous ECG monitoring for assessment of first AF recurrence and AF burden using an implantable cardiac monitor,
-
Regular echocardiographic exams for reverse atrial remodelling assessment,
-
HRQoL questionnaires
-
Assessment of cognitive function
-
Atrial fibrillation evaluation regarding structured characterisation and AF progression/regression
-
Assessment of Health care use and costs
-
Safety
详细描述
The primary goal is to evaluate if early pulmonary vein isolation (PVI) performed with the Arctic Front cryoballoon as first-line therapy is superior to antiarrhythmic drugs (AAD) in preventing atrial arrhythmia recurrences in patients with persistent atrial fibrillation (AF).
The main secondary goal is to evaluate the impact of early invasive intervention on health related quality of life (HRQOL) and symptoms, and on safety in comparison to primary AAD therapy, using generic and disease-specific HRQOL questionnaires and also assess Quality Adjusted Life Years (QALYs) score and EHRA classification of symptoms.
The third goal is to assess the impact of an early intervention on cardiovascular health care use and its relation to AF/AT burden and to assess treatment burden and cost-effectiveness compared to AAD.
Study Design: Multicentre, prospective 1:1 randomized open blinded for evaluation of end point (PROBE) controlled parallel-group superiority trial comparing first-line pulmonary vein isolation (PVI) using the cryoballoon (Arctic Front AdvanceR, Medtronic) and first-line antiarrhythmic drug (AAD) therapy. Patients will be randomized 1:1 to first-line PVI using the cryoballoon or to first-line AAD therapy. A 1:1 block randomization immediately after implantation of an implantable cardiac monitor (ICM ) before run-in.
After fulfilling inclusion criteria and no exclusion criteria, an ICM (Reveal Linq™, Medtronic, Inc., Minneapolis, MN) will be injected subcutaneously for continuous rhythm monitoring during a 2 months "run-in" period prior initiation of allocated treatment, and then during 3 years of follow up. A 6 minutes detection cut-off for AF will be used. Patients and physicians will be blinded to the ICM result. Three month blanking period after treatment will not be included in the analysis. SAEs detected via ICM will be managed independently from the blinding of AF. If the ICM has to be explanted the patient should continue in the study with alternative monitoring tool as defined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The randomised treatment is open but the outcomes are blinded.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-longstanding persistent symptomatic AF with at least 2 episodes within last 24 months, the latest episode within the previous 6 months and one documented on a 12 lead ECG or Holter monitor, that is classified as either
- •Classical persistent AF (continuously sustained beyond 7 days and <12 months in duration) as defined by ESC guidelines14 OR
- •Persistent AF which has progressed from paroxysmal AF (patients who have been cardioverted within 7 days of onset provided a history of spontaneous conversion to sinus rhythm is lacking during the past 24 months).
- •Candidate for rhythm control therapy; AF ablation or AAD based on symptomatic AF.
排除标准
- •Regular daily use of AAD class I or III at adequate therapeutic dosages (pill-in-the-pocket permitted, beta-blockers permitted).
- •Previous AF ablation or surgery.
- •Severe heart failure (NYHA III-IV).
- •Reduced left ventricular ejection fraction (LVEF ≤40 % during sinus rhythm).
- •Hypertrophic cardiomyopathy (septal or posterior wall thickness >1.5 cm)
- •Severely enlarged LA with left atrial volume indexed to body surface area (LAVI, ml/m2) >
- •Significant valvular disease requiring treatment or valve prothesis.
- •Severe Chronic Obstructive Pulmonary Disease (COPD) stage III or chronic kidney disease (eGFR< 30 umol/l)).
- •Planned cardiac intervention within the next 12 months or cardiac surgery last 6 months.
- •Myocardial infarction, revascularisation previous 6 months.
- •Stroke or Transient Ischemic Attack (TIA) within previous 6 months.
- •Tachycardiomyopathy.
- •Dependent on VVI (ventricular single chamber inhibited) pacing.
- •Conventional contraindications for AF ablation including AF due to reversible causes and contraindications for both class IC and class III antiarrhythmic drugs.
- •Expected survival less than 3 years, alcohol or drug abuse.
- •Participation in another trial or absence of consent.
研究组 & 干预措施
Cryoballoon pulmonary vein isolation
Cryoballoon (Arctic Front AdvanceR, Medtronic) for pulmonary vein isolation
干预措施: Pulmonary vein isolation (Device)
Antiarrhythmic drug
Tablet Dronedarone:- 400 mg twice daily or Tablet Flecainide:- (50-)100 (-200) mg twice daily or slow release (100-)200 mg once daily.
If these drugs fail or give side effects:
Tablet Propafenone:- 150 mg 3 times daily increasing to 300 mg twice daily, if necessary max 300 mg three times daily. Dose reduction for patients <70 kg bodyweight.
Tablet Sotalol:- 80 mg twice daily up to 160 mg twice daily. Dose reduction to half dosage if a creatinine clearance is 30-60 ml/min.
干预措施: dronedarone - Multaq™ OR flecainide - Tambocor™ OR propafenone - Rytmonorm™ OR sotalol - Sotacor™ (Drug)
结局指标
主要结局
Proportion of patients free from first atrial tachyarrhythmia recurrence lasting 6 minutes or longer
时间窗: 12 months after initiation of allocated treatment excluding the first 3 months blanking period
In the absence of antiarrhythmic drugs in ablation group as documented by an implantable cardiac monitor from initiation of treatment.
次要结局
- Cognitive function(baseline,12, 24, 36 months after initiation of treatment)
- Cost-effectiveness analysis by EuroQol-5 Dimensions (EQ-5D)(36 months)
- Proportion of patients free from ECG documented atrial tachyarrhythmia recurrence lasting 6 minutes or longer after the 1st and last ablation procedure respectively(36 months)
- Total atrial arrhythmia burden (percentage of time in AF/AT)(baseline,12, 24, 36 months after initiation of treatment excluding the 3 months blanking period)
- AF progression and reversion(baseline,12, 24, 36 months follow-up excluding 3 months blanking period)
- Rate of Healthcare utilizations for cardiovascular reasons(baseline,12, 24, 36 months after initiation of treatment excluding the 3 months blanking period)
- Generic Health Related Quality of life (HRQoL)(baseline, 12, 24, 36 months follow-up)
- Symptoms(baseline, 12, 24, 36 months after initiation of treatment)
- AF specific Health Related Quality of Life(baseline, 12, 24, 36 months after initiation of treatment excluding the 3 months blanking period)
- Covariate adjusted primary endpoint freedom from first atrial tachyarrhythmia recurrence lasting 6 minutes or longer(12 and 36 months)
- Numbers of withdrawals / 'cross-overs'(12, 24, 36 months)
- Proportion of patients with Reverse atrial remodeling(baseline, 12, 24 and 36 months)
- Adverse events(12, 24, 36 months)
研究者
Carina Blomstrom Lundqvist, MD, PhD
Senior Consultant, Professor
Region Örebro County