Interventional Strategies in Treatment of Atrial Fibrillation: Percutaneous Closure of the Left Atrial Appendage Versus Catheter Ablation (ISAR-AF)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, associated with an increased risk of morbidity and mortality1. The management of AF patients is aimed at reducing symptoms and at preventing severe complications associated with AF. In the last years, two new strategies have emerged with different objectives. In the PROTECT AF study2, percutaneous closure of the Left Atrial Appendage (LAA) with a closure device provided an alternative strategy to oral anticoagulation for stroke prophylaxis. The AFFIRM trial3 has shown that drug-based management of AF with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiovascular mortality and might be associated with an increased noncardiovascular death rate4. Catheter ablation has gained a greater place in the rhythm control strategy, showing superiority in maintaining sinus rhythm in comparison with AAD5. However, in persistent AF, repeat ablation procedures are necessary in up to 70% of patients to achieve sinus rhythm at a long-term follow-up6-7.

This prospective, randomized trial will compare the percutaneous closure of the LAA combined with a rate-control strategy to catheter ablation in the management of patients with persistent AF. Patients who are eligible for catheter ablation as well as LAA closure device implantation and are willing to participate in the study will be randomly assigned to catheter ablation or percutaneous closure of the LAA by a closure device implantation in the relation 1:1. The primary endpoint of the study is a composite endpoint at 12 months of all cause death, thrombo-embolic events, major bleeding (BARC type 3), re-hospitalisation and severe symptoms due to arrhythmias. Secondary endpoints include a composite endpoint of bleeding, a composite endpoint of thrombo-embolic events, cardio-vascular mortality, total duration of hospitalisation, sustained discontinued anticoagulation, quality of life improvement, use of Antiarrhythmic Drugs (AAD), total costs, freedom from arrhythmia and average ventricular frequency in 7-day holter ECG at 12 months.

The objective of the study is to assess the superiority of percutaneous closure of the LAA combined with rate-control to catheter ablation in patients with oligosymptomatic AF.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Percutaneous closure of LAA; Procedure: Catheter ablation of AF

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 80636
    • Deutsches Herzzentrum München

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with oligosymptomatic AF eligible for both interventions (CA and LAA closure device implantation).
2. Written, informed consent by the patient or her/his legally-authorized representative for participation in the study.
3. In women with childbearing potential a negative pregnancy test is mandatory.

Exclusion Criteria:

1. Left atrial thrombus
2. Other indication than AF for oral anticoagulation (valve prosthesis, pulmonary embolism, recurrent vein thrombosis)
3. Contraindication for oral anticoagulation
4. Severe valvular heart disease
5. Severe left ventricular systolic function (ejection fraction<30%)
6. Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) with life expectancy less than 12 months or that may result in protocol non-compliance.
7. Pregnancy (present, suspected or planned) or positive pregnancy test.
8. Patient's inability to fully cooperate with the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Percutaneous closure of LAA	Procedure: Percutaneous closure of LAA; Percutaneous closure of LAA
Active Comparator: Catheter ablation of AF	Procedure: Catheter ablation of AF; Catheter ablation of AF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A 12-month composite endpoint of all cause death, thrombo-embolic events, major bleeding BARC type III, re-hospitalisation and severe symptoms due to arrhythmias	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Quality of Life	12 months
The individual components of the primary endpoint	12 months
Discontinuation of anticoagulation	12 months
Use of Antiarrhythmic Drugs	12 months
freedom from symptomatic arrhythmia	12 months

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen
• Investigators: Study Chair: Albert Schömig, MD, Deutsches Herzzentrum München; Principal Investigator: Steffen Massberg, MD, Deutsches Herzzentrum München; Principal Investigator: Isabel Deisenhofer, MD, Deutsches Herzzentrum München; Study Director: Sonia Ammar, MD, Deutsches Herzentrum München; Study Director: Julia Goedel, MD, Deutsches Herzzentrum München

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: November 25, 2010
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 2, 2011

Study Record Updates

• Last Update Posted (Actual): April 11, 2017
• Last Update Submitted That Met QC Criteria: April 10, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: atrial fibrillation; intervention; catheter ablation; percutaneous closure of LAA
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: GER-EP-006