Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery

NCT ID: NCT00903370

Last Updated: 2017-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2015-09-30

Brief Summary

The purpose of the research is to determine whether treating atrial fibrillation with surgical ablation during scheduled mitral valve surgery is better than mitral valve surgery by itself without the surgical ablation. Surgical ablation of atrial fibrillation is a technique used by surgeons to deaden atrial heart tissue and block electrical signals that may be causing your heart to beat irregularly. There are no new procedures being tested in this study; both mitral valve surgery and surgical ablation are used regularly in patients who have mitral valve problems and atrial fibrillation, although no surgical ablation devices have been approved by the Food and Drug Administration for the treatment of atrial fibrillation. What is not known with certainty, is whether patients with atrial fibrillation who are having planned mitral valve surgery would do better if they also had surgical ablation rather than medication alone to treat their atrial fibrillation.

Detailed Description

The purpose of this study is to determine whether the addition of surgical ablation to planned mitral valve surgery for patients with persistent or longstanding persistent AF (within 6 months prior to randomization) reduces the incidence of postoperative heart arrhythmia compared to mitral valve repair with medication therapy alone. This is a randomized, multi-center trial which will enroll 260 subjects who will be randomized in a 1:1 fashion to: (a) mitral valve surgery plus surgical ablation or (b) mitral valve surgery without ablation (control group). All patients will undergo ligation or excision of the left atrial appendage. Patients assigned to the ablation group will be further randomized (1:1) to one of two lesion sets: (1) pulmonary vein isolation only or (2) biatrial Maze lesions. The target population for this trial consists of adult patients with mitral valve disease requiring surgical intervention and persistent or longstanding persistent atrial fibrillation. All patients who meet the eligibility criteria may be included in the study regardless of gender, race or ethnicity. The primary efficacy endpoint is freedom from AF, which will be measured by 3-day continuous monitoring at 6 months and 12 months post-ablation. The primary safety endpoint is a composite of death, stroke, serious cardiac events (heart failure, myocardial infarction), cardiac re-hospitalizations, transient ischemic attack, pulmonary embolism, peripheral embolism, excessive bleeding, deep sternal wound infection/mediastinitis, damage to specialized conduction system requiring permanent pacemaker, damage to peripheral structures, such as the esophagus, within 30 days post-procedure or hospital discharge (whichever is later).

Conditions

Atrial Fibrillation; Mitral Valve Insufficiency; Mitral Valve Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

MVS

All participants will undergo mitral valve surgery with ligation/excision of left atrial appendage.

Group Type: ACTIVE_COMPARATOR

MVS

Intervention Type: PROCEDURE

All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.

Ablation

Participants will undergo mitral valve surgery with ligation/excision of left atrial appendage plus surgical ablation with pulmonary vein isolation or biatrial lesion set.

Group Type: EXPERIMENTAL

MVS

Intervention Type: PROCEDURE

All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.

Ablation

Intervention Type: DEVICE

For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include, the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture is noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture is noted, additional ablations on the atrial cuff will be performed until isolation is confirmed. This will be repeated on the left pulmonary veins.

Interventions

MVS

All participants will have their left atrial appendage excised or excluded. For mitral regurgitation, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, and for most cases of mitral stenosis, a valve replacement will be performed.

Intervention Type: PROCEDURE

Ablation

For participants treated by pulmonary vein isolation, two separate encircling lesions will be made around the left and right pulmonary veins. For participants treated with biatrial maze lesion set, the left atrial lesions will include, the two encircling lesions, as well as connecting lesions between to the pulmonary veins, from the pulmonary veins to the mitral valve annulus, and from the pulmonary veins to the left atrial appendage. The right pulmonary veins will be isolated first. Isolation will be confirmed by pacing the pulmonary veins at the previously identified threshold for capture. If no atrial capture is noted, it will be inferred that the right pulmonary veins were isolated. If atrial capture is noted, additional ablations on the atrial cuff will be performed until isolation is confirmed. This will be repeated on the left pulmonary veins.

Intervention Type: DEVICE

Other Intervention Names

Mitral Valve Repair; Mitral Valve Replacement; Surgical Ablation

Eligibility Criteria

Inclusion Criteria

• Able to sign Informed Consent and Release of Medical Information forms
• Age ≥ 18 years
• Clinical indications for mitral valve surgery for the following:

1. Organic mitral valve disease; or

2. Functional non-ischemic mitral regurgitation; or

3. Ischemic mitral regurgitation with evidence of concomitant structural mitral valve disease

Note: May include need for surgical management of functional tricuspid regurgitation or patent foramen ovale. May also include concomitant CABG, aortic arch or aortic valve procedure. Surgical intervention may be performed via sternotomy or minimally invasive procedure.

• a) Persistent AF within 6 months prior to randomization, defined as non self-terminating AF lasting greater than 7 days but no more than one year, or lasting less than 7 days but necessitating pharmacologic or electrical cardioversion.

• Duration of AF must be documented by medical history and
• Presence of AF must be documented by a direct electrocardiographic assessment within 6 months prior to randomization.
• b) Longstanding persistent AF is defined as continuous AF of greater than one year duration.

• Duration of AF must be documented by medical history and
• Presence of AF must be documented by a direct electrocardiographic assessment upon arrival in the OR.
• Able to use heart rhythm monitor

Exclusion Criteria

• 1. AF without indication for mitral valve surgery 2. AF is paroxysmal 3. Evidence of left atrial thrombus by intra-operative TEE 4. Evidence of active infection 5. Mental impairment or other conditions that may not allow subject to understand the nature, significance, and scope of study 6. Surgical management of hypertrophic obstructive cardiomyopathy 7. Previous catheter ablation for AF 8. Life expectancy of less than one year 9. Absolute contraindications for anticoagulation therapy 10. Enrollment in concomitant drug or device trials 11. Uncontrolled hypo- or hyperthyroidism 12. FEV1 < 30% of predicted value and/or need for home oxygen therapy 13. Women who are pregnant as evidenced by positive pregnancy test 14. Women of childbearing age who do not agree to be on adequate birth control throughout the period of the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Annetine Gelijns

OTHER

Sponsor Role: lead

Responsible Party

Annetine Gelijns

Professor of Health Policy, Chair Department of Health Evidence & Policy

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Timothy Gardner, MD

Role: STUDY_CHAIR

Christiana Care Health Services

Patrick O'Gara, MD

Role: STUDY_CHAIR

Brigham and Women's Hospital

Annetine C. Gelijns, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Yale New Haven Hospital

New Haven, Connecticut, United States

Christiana Care Health Services

Newark, Delaware, United States

Emory University

Atlanta, Georgia, United States

University of Maryland

Baltimore, Maryland, United States

NIH Heart Center at Suburban Hospital

Bethesda, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mount Sinai School of Medicine

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Einstein Heart Center

The Bronx, New York, United States

Duke University

Durham, North Carolina, United States

East Carolina Heart Institute

Greenville, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor Research Institute

Plano, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

University of Alberta Hospital

Edmonton, Alberta, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Quebec Heart Institute/Laval Hopital

Québec, Quebec, Canada

Countries

United States; Canada

References

Gillinov AM, Gelijns AC, Parides MK, DeRose JJ Jr, Moskowitz AJ, Voisine P, Ailawadi G, Bouchard D, Smith PK, Mack MJ, Acker MA, Mullen JC, Rose EA, Chang HL, Puskas JD, Couderc JP, Gardner TJ, Varghese R, Horvath KA, Bolling SF, Michler RE, Geller NL, Ascheim DD, Miller MA, Bagiella E, Moquete EG, Williams P, Taddei-Peters WC, O'Gara PT, Blackstone EH, Argenziano M; CTSN Investigators. Surgical ablation of atrial fibrillation during mitral-valve surgery. N Engl J Med. 2015 Apr 9;372(15):1399-409. doi: 10.1056/NEJMoa1500528. Epub 2015 Mar 16.

Reference Type: RESULT

PMID: 25853744 (View on PubMed)

DeRose JJ Jr, Mancini DM, Chang HL, Argenziano M, Dagenais F, Ailawadi G, Perrault LP, Parides MK, Taddei-Peters WC, Mack MJ, Glower DD, Yerokun BA, Atluri P, Mullen JC, Puskas JD, O'Sullivan K, Sledz NM, Tremblay H, Moquete E, Ferket BS, Moskowitz AJ, Iribarne A, Gelijns AC, O'Gara PT, Blackstone EH, Gillinov AM; CTSN Investigators. Pacemaker Implantation After Mitral Valve Surgery With Atrial Fibrillation Ablation. J Am Coll Cardiol. 2019 May 21;73(19):2427-2435. doi: 10.1016/j.jacc.2019.02.062.

Reference Type: DERIVED

PMID: 31097163 (View on PubMed)

Related Links

http://www.ctsurgerynet.org

Click here for the Cardiothoracic Surgical Trials Network Web site

Other Identifiers

U01HL088942

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL088942-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

656

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 08-1078-0004

Identifier Type: -

Identifier Source: org_study_id