CASTLE-AF: Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF

Sponsor

Biotronik SE & Co. KG (Industry)

Overall Status

Completed

CT.gov ID

NCT00643188

Collaborator

(none)

398

Enrollment

Locations

Arms

110

Actual Duration (Months)

12.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. The incidence and prevalence of AF increase exponentially with increasing age and AF is associated with higher mortality, more frequent hospitalization, and lower quality of life. Furthermore, AF is often associated with heart failure. The majority of AF is initiated by ectopic foci found primarily in the pulmonary veins. It was shown that catheter ablation of those veins could eliminate episodes of AF. In patients with heart failure, catheter ablation could improve cardiac function, symptoms and quality of life. It remains still unknown whether AF ablation is more effective than conventional treatment in terms of mortality and morbidity.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Heart Failure	Procedure: Radiofrequency ablation Other: Conventional treatment	Phase 4

Detailed Description

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice; its incidence and prevalence increase exponentially with increasing age and it is associated with increased mortality, more frequent hospitalization, and decreased quality of life.

An initial approach to the cure of patients suffering from AF was surgical intervention with the Maze procedure, which involved the creation of linear lesions in the atria to break the re-entrant wavefronts responsible for maintenance of AF. Subsequently, less invasive procedures have been developed to achieve the same results. One of them is catheter based radio frequency ablation, in which a catheter is placed in the heart percutaneously, followed by application of electrical energy to the target regions, thereby creating a permanent lesion.

The origin of AF is often localized in the pulmonary veins (PVs); therefore one common approach is to ablate them in order to electrically isolate them from the left atrium (LA). Several strategies have been developed, such as linear, segmental, circumferential, and double-lasso.

Additionally, other anatomical regions such as the right atrium (RA), superior vena cava (SVC), and coronary sinus (CS) can be ablated in order to eliminate non-PV drivers of AF.

Heart failure (HF) is frequently a chronic and lethal condition, causing substantial morbidity and, after initial diagnosis, results in mortality rates which come close to or exceed those of many malignancies.

Both AF and HF have a significant impact on the health care expenditures. The two diseases often coexist, there is a complex interaction between them: many of the processes that predispose to HF, such as hypertension, diabetes, coronary artery disease, and valvular heart disease, are also risk factors for the development of AF. Similarly, many of the echocardiographic findings that are common in patients with HF, including LA enlargement, increased left ventricular (LV) wall thickness, and reduced LV fractional shortening, predispose patients in the development of AF.

In small groups of patients suffering from HF and AF, radio frequency ablation has been performed; the restoration of sinus rhythm resulted in the improvement of quality of life, exercise performance, and cardiac parameters like ejection fraction and fractional shortening. It is still unknown if such therapy is also effective in reducing mortality and morbidity.

CASTLE-AF is a prospective, unblinded, randomized, multicenter study whose aim is to compare the effect of radio frequency catheter-based ablation on mortality and morbidity with that of conventional treatment in HF subjects with AF. About 420 patients with LV dysfunction (ejection fraction ≤ 35%) and New York Heart Association (NYHA) class ≥ II, already implanted with a dual chamber implantable cardioverter defibrillator (ICD) with Home Monitoring® capabilities, will be enrolled and randomized 1:1 to undergo either AF ablation or standard treatment as indicated in the American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology (ESC) 2006 guidelines for the management of patients with AF. In addition to planned and unplanned visits, the ablated patients will be constantly monitored remotely via Home Monitoring®, in order to detect any recurrences of AF episodes, even if non-symptomatic or short in duration, during an observational period of minimum 3 years for each patient.

Study Design

Study Type:

Interventional

Actual Enrollment :

398 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Catheter Ablation Versus Standard Conventional Treatment in Patients With Left Ventricular Dysfunction and Atrial Fibrillation

Actual Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Mar 1, 2017

Actual Study Completion Date :

Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Radiofrequency ablation of atrial fibrillation: Subjects assigned to the catheter AF ablation strategy will undergo ablation within 48 hours after baseline evaluation. The aim of the procedure is to achieve isolation of all Pulmonary Veins (PVs) and to restore sinus rhythm. Only radiofrequency catheter based AF ablation is permitted; other methods, like cryoablation, ultrasound and laser, are not permitted in this study. Before ablation, a transesophageal echocardiogram must be performed in order to rule out presence of atrial thrombi. Anticoagulation should be initiated, or continued, for at least six months post ablation. Six months after successful ablation and in absence of any recurrence of AF, antiarrhythmic drugs should be discontinued.	Procedure: Radiofrequency ablation Radiofrequency ablation of atrial fibrillation
Active Comparator: 2 Conventional treatment: Subjects assigned to the conventional treatment strategy will be treated according to current guidelines for the management of patients with chronic heart failure and/or atrial fibrillation. Efforts to maintain sinus rhythm in this study arm are recommended. Anticoagulation will be initiated, if not already started, and maintained throughout the study according to current guidelines.	Other: Conventional treatment The best medical treatment according to the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult and the ACC/AHA/ESC 2006 Guidelines for Management of Patients with Atrial Fibrillation.

Arm

Intervention/Treatment

Experimental: 1

Radiofrequency ablation of atrial fibrillation: Subjects assigned to the catheter AF ablation strategy will undergo ablation within 48 hours after baseline evaluation. The aim of the procedure is to achieve isolation of all Pulmonary Veins (PVs) and to restore sinus rhythm. Only radiofrequency catheter based AF ablation is permitted; other methods, like cryoablation, ultrasound and laser, are not permitted in this study. Before ablation, a transesophageal echocardiogram must be performed in order to rule out presence of atrial thrombi. Anticoagulation should be initiated, or continued, for at least six months post ablation. Six months after successful ablation and in absence of any recurrence of AF, antiarrhythmic drugs should be discontinued.

Procedure: Radiofrequency ablation

Radiofrequency ablation of atrial fibrillation

Active Comparator: 2

Conventional treatment: Subjects assigned to the conventional treatment strategy will be treated according to current guidelines for the management of patients with chronic heart failure and/or atrial fibrillation. Efforts to maintain sinus rhythm in this study arm are recommended. Anticoagulation will be initiated, if not already started, and maintained throughout the study according to current guidelines.

Other: Conventional treatment

The best medical treatment according to the ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult and the ACC/AHA/ESC 2006 Guidelines for Management of Patients with Atrial Fibrillation.

Outcome Measures

Primary Outcome Measures

All-cause mortality or worsening heart failure requiring unplanned hospitalization [7 years]

Secondary Outcome Measures

All-cause mortality Cardiovascular mortality Unplanned hospitalization due to cardiovascular reason Worsening heart failure requiring unplanned hospitalization Cerebrovascular accidents Left ventricular function Exercise tolerance Quality of life [7 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Symptomatic paroxysmal or persistent atrial fibrillation
Failure or intolerance of antiarrhythmic drug therapy or unwillingness to take antiarrhythmic drugs
Left Ventricular Ejection Fraction <= 35%
NYHA >= II
ICD for primary or secondary prevention with atrial sensing capabilities or Cardiac Resynchronization Therapy plus Defibrillator (CRT-D) device, both with Home Monitoring® technology already implanted
Patient is willing and able to comply with the protocol and has written informed consent
Age >= 18 years

Exclusion Criteria:

Contraindication for chronic anticoagulation therapy and heparin
Documented left atrial diameter > 6 cm
Previous left heart ablation procedure for atrial fibrillation
Acute coronary syndrome, cardiac surgery, angioplasty or stroke within 2 months prior to enrollment
Untreated hypothyroidism or hyperthyroidism
Enrollment in another investigational drug or device study
Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertility age
Mental or physical inability to take part in the study
Listed for heart transplant
Cardiac assist device implanted
Planned cardiovascular intervention
Life expectancy ≤ 12 months
Uncontrolled hypertension
Requirement for dialysis due to terminal renal failure
Participation in another telemonitoring concept

Contacts and Locations

Locations

	Site	City	Country
1	Royal Adelaide Hospital	Adelaide	Australia
2	Royal Brisbane and Women's Hospital	Herston	Australia
3	A. ö. Krankenhaus der Elisabethinen Linz	Linz	Austria
4	Allgemeines Krankenhaus der Stadt Wien	Wien	Austria
5	Herz- und Diabeteszentrum Nordrhein-Westfalen	Bad Oeynhausen	Germany
6	Charité Campus Mitte	Berlin	Germany
7	Charité Campus Virchow-Klinikum	Berlin	Germany
8	Franz-Volhard-Klinik, Universitätsklinikum Charité	Berlin	Germany
9	Vivantes-Klinikum am Urban	Berlin	Germany
10	Städtische Kliniken Bielefeld	Bielefeld	Germany
11	St. Marien Hospital	Bonn	Germany
12	Zentralkrankenhaus Links der Weser, Siebels & Langes Partnerschaft	Bremen	Germany
13	Klinikum Coburg	Coburg	Germany
14	Evangelisches Krankenhaus Düsseldorf	Düsseldorf	Germany
15	Kardiocentrum Frankfurt an der Klinik Rotes Kreuz	Frankfurt am Main	Germany
16	Universitätsklinikum der Ernst-Moritz-Arndt-Universität Greifswald	Greifswald	Germany
17	Krankenhaus Landshut-Achdorf	Landshut	Germany
18	Klinikum Lüdenscheid	Lüdenscheid	Germany
19	Deutsches Herzzentrum München	München	Germany
20	St. Vincenz-Krankenhaus	Paderborn	Germany
21	Universitätsklinikum Rostock	Rostock	Germany
22	Semmelweis Medical University	Budapest	Hungary
23	The Debrecen University of Medicine	Debrecen	Hungary
24	Antonius Ziekenhuis	Nieuwegein	Netherlands
25	Erasmus Medical Center	Rotterdam	Netherlands
26	Isala Klinieken	Zwolle	Netherlands
27	National Institute of Cardiology	Warszawa	Poland
28	HRD Surgical Department; Federal Centre of Cardiovascular Surgery	Krasnoyarsk	Russian Federation
29	N.S.B.R.I. of Circulation Pathology	Novosibirsk	Russian Federation
30	Arrhythmology Department; Federal Heart Blood and Endocrinology Center n.a. V. A. Almazov	Saint Petersburg	Russian Federation
31	FSBI Research Institute of Cardiology, Siberian Branch of RAMS	Tomsk	Russian Federation
32	The Heart Hospital	London	United Kingdom

Sponsors and Collaborators

Biotronik SE & Co. KG

Investigators

Study Chair: Johannes Brachmann, Prof. Dr., Klinikum Coburg, Germany
Study Chair: Nassir F. Marrouche, Dr., Division of Cardiology, University of Utah Health Sciences Cente, Salt Lake City, Utah, United States