aMAZE Study: LAA Ligation Adjunctive to PVI for Persistent or Longstanding Persistent Atrial Fibrillation (aMAZE)

Left Atrial Appendage Ligation With the LARIAT™ Suture Delivery System as Adjunctive Therapy to Pulmonary Vein Isolation for Persistent or Longstanding Persistent Atrial Fibrillation

This study is a prospective, multicenter, randomized (2:1) controlled study to evaluate the safety and effectiveness of the LARIAT System to percutaneously isolate and ligate the Left Atrial Appendage from the left atrium as an adjunct to planned pulmonary vein isolation (PVI) catheter ablation in the treatment of subjects with symptomatic persistent or longstanding persistent atrial fibrillation.

This study will be conducted in two stages:

• Limited Early Stage (Stage 1): up to 250 subjects at up to 65 sites. (COMPLETED, transitioned to Stage 2)
• Pivotal Stage/ Phase III (Stage 2): up to 600 subjects at up to 65 sites. (COMPLETED) All subjects from both stages will be included in the primary analysis.

Study Overview

• Status: Active, not recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Device: LARIAT + PVI; Device: Pulmonary Vein Isolation

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Cardiovascular Research Group
    • Phoenix, Arizona, United States, 85013
      • Arizona Arrhythmia Research Center
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Santa Barbara, California, United States, 93103
      • Santa Barbara Cottage Hospital
    • Stanford, California, United States, 94305
      • Stanford University
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Jacksonville, Florida, United States, 32204
      • St. Vincent's Healthcare
  • Georgia
    • Athens, Georgia, United States, 30606
      • Piedmont Athens Regional Cardiology
    • Atlanta, Georgia, United States, 30342
      • Emory University Hospital
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • The Queen's Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University / Bluhm Cardiovascular Institute
    • Maywood, Illinois, United States, 60153
      • Loyola University Center for Heart and Vascular Medicine
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
    • Springfield, Illinois, United States, 62769
      • Prairie Education and Research Cooperative
    • Winfield, Illinois, United States, 60190
      • Northwestern Medicine Central DuPage Hospital
  • Indiana
    • Munster, Indiana, United States, 46321
      • Community Hospital
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
    • Overland Park, Kansas, United States, 66215
      • Kansas City Cardiac Arrhythmia Research
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Cardiovascular Institute of the South Clinical Research Corporation
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Michigan
    • Marquette, Michigan, United States, 49855
      • UP Health System- Marquette
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • DaVita Medical Group
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Heart Institute
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Brooklyn, New York, United States, 11219
      • Maimonides Medical Center
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
    • Columbus, Ohio, United States, 43214
      • The Ohio Health Research Institute
  • Oregon
    • Medford, Oregon, United States, 97504
      • Southern Oregon Cardiology
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Medical Specialists Association / Bryn Mawr Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Trident Medical Center
    • Charleston, South Carolina, United States, 29466
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Research Foundation
    • Austin, Texas, United States, 78756
      • Austin Heart
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Houston, Texas, United States, 77030
      • Baylor - St. Luke's Medical Center
    • Plano, Texas, United States, 75093
      • Baylor Plano Scott & White Research Institute Heart Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • Tyler, Texas, United States, 75701
      • Christus Trinity Mother Frances Health System
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented diagnosis of symptomatic continuous persistent or longstanding persistent non-valvular atrial fibrillation
• Failed at least one Class I or III Antiarrythmic drug (AAD) and therefore, eligible and intended for standard of care catheter ablation;
• Life expectancy ≥ 1 year;
• Willing and able to return to and comply with scheduled follow-up visits and tests; and
• Willing and able to provide written informed consent

Exclusion Criteria:

• Prior procedure involving opening of the pericardium or entering the pericardial space (e.g., coronary artery bypass graft, heart transplantation, valve surgery) where adhesions are suspected;
• Any prior epicardial ablation or any type of left-sided atrial ablation procedure;
• LA diameter > 6 cm as measured by computerized tomography and confirmed by the imaging core laboratory;
• Documented embolic stroke, transient ischemic attach or suspected neurologic event within 3 months prior to the planned study intervention;
• Currently exhibits New York Heart Association Class IV heart failure symptoms;
• Documented history of right heart failure specifically when right ventricle exceeds the left ventricular size;
• Documented history of myocardial infarction (MI) within 3 months prior to the planned study intervention;
• Documented history of unstable angina within 3 months prior to the planned study intervention;
• Documented history of cardiogenic shock, hemodynamic instability or any medical condition in which intra-aortic balloon pump (IABP) therapy is clinically indicated within 3 months prior to the planned study intervention;
• Documented symptomatic carotid disease, defined as > 70% stenosis or > 50% stenosis with symptoms;
• Diagnosed active local or systemic infection, septicemia or fever of unknown origin at tme of baseline screening;
• Chronic renal insufficiency defined as eGFR < 30 mL/min/1.73m2 within 3 months prior to planned study intervention;
• End Stage Renal Disease (ESRD) or documented history of renal replacement / dialysis;
• Current documented history of clinically significant liver disease which predisposes the subject to significant bleeding risk (clinically defined by the treating physician);
• Any history of thoracic radiation with the exception of localized radiation treatment for breast cancer;
• Current documented use of long-term treatment with oral corticoid steroids, not including use of inhaled steroids for respiratory diseases;
• Active pericarditis;
• Active endocarditis;
• Any documented history or autoimmune disease associated with pericarditis;
• Evidence of Pectus Excavatum (documented and clinically defined by the treating physician);
• Untreated severe scoliosis (documented and clinically defined by treating physician);
• Documented Left Ventricular Ejection Fraction (LVEF) < 30% within 30 days prior to planned intervention;
• Documented presence of implanted congenital defect closure devices, (e.g., atrial septal defect, patent foramen ovale or ventricular septal defect device);
• Previously attempted occlusion of the left atrial appendage (by any surgical or percutaneous method);
• Inability, or unwillingness or contraindication to undergo TEE or CTA imaging or 24-hour Holter monitoring;
• Body Mass Index (BMI) > 40;
• Evidence of active Graves disease;
• Current untreated hypothyroidism;
• Any contraindication to suture, endovascular device, or other minimally invasive techniques including percutaneous, transseptal, and/or sub-xiphoid access;
• Subject is pregnant or plans / desires to get pregnant within next 12 months;
• Current enrollment in an investigation or study of an investigational device or investigational drug that would interfere with this study and the required follow up;
• Mental impairment or other psychiatric conditions which may not allow patient to understand the nature, significance and scope of the study;
• Any other criteria, medical illness or comorbidity which would make the subject unsuitable to participate in this study as determined by the clinical site Primary Investigator;

Additional Exclusion Criteria: Based on Screening / Pre-procedure Imaging

Subjects will also be excluded if they meet any of the following:

• Based on screening computed tomography angiography performed within 90 days prior to study intervention as confirmed by the core lab:

  • Left atrial appendage morphology: Superior-posterior oriented left atrial appendage (i.e. superior C shape), that has Left atrial appendage distal apex extending posterior to the ostium of the appendage.
  • Left atrial appendage positioned behind the pulmonary artery; or
  • All other left atrial morphology: Left atrial appendage LARIAT approach width > 50 mm.

• Based on a peri-procedural imaging (transesophageal echocardiography) at time of LARIAT or catheter ablation) and confirmed by institution's designated LARIAT echocardiographer:

  • Intracardiac thrombus; or
  • Significant mitral valve stenosis (i.e., mitral valve stenosis < 1.5cm2)

NOTE: It is anticipated that a majority of subjects enrolled in the aMAZE Trial will be elderly US Medicare beneficiaries. Therefore, the results from the aMAZE Trial are expected to be generalizable to the Medicare population.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LARIAT + PVI Treatment Group; Percutaneously isolate and ligate the Left Atrial Appendage (LAA) from the left atrium (LA) with the LARIAT System prior to planned pulmonary vein isolation (PVI) catheter ablation	Device: LARIAT + PVI; Left Atrial Appendage ligation with the LARIAT System initially performed followed by adjunctive pulmonary vein isolation catheter ablation in staged procedures; Other Names: Left Atrial Appendage ligation + Pulmonary Vein Isolation; Device: Pulmonary Vein Isolation; Perform pulmonary vein isolation (PVI) catheter ablation procedure using a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.
ACTIVE_COMPARATOR: PVI Catheter Ablation Group; Perform pulmonary vein isolation (PVI) catheter ablation procedure using a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.	Device: Pulmonary Vein Isolation; Perform pulmonary vein isolation (PVI) catheter ablation procedure using a contact force sensing, irrigated radiofrequency catheter approved by FDA for the treatment of atrial fibrillation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from episodes of atrial fibrillation > 30 seconds at 12 months post index pulmonary vein isolation	Measured by 24-hour Holter Monitoring	12 months following Pulmonary Vein Isolation catheter ablation procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from any atrial fibrillation/atrial tachycardia/atrial flutter recurrence defined as any episode > 30 seconds with or without AAD	Measured by 24-hour Holter Monitoring	Following the 90 day blanking period through 12 months post-index pulmonary vein isolation
Composite endpoint of stroke of any cause and systemic embolism as adjudicated by the clinical events committee		12 months following index pulmonary vein isolation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
LARIAT Technical Success	Successful placement of the LARIAT device pre-tied suture around the left atrial appendage to achieve left atrial appendage ligation defined as ≤1 ± 1mm diameter residual communication w/ left atrium, as assessed by transesophageal echocardiography	Immediately post-LARIAT ligation (acute) and at 12 months following index pulmonary vein isolation

Collaborators and Investigators

• Sponsor: AtriCure, Inc.
• Investigators: Study Chair: David J Wilber, MD, Loyola University Department of Medicine; Study Chair: Dhanunjaya Lakkireddy, MD, Kansas City Cardiac Arrhythmia Research

Publications and helpful links

General Publications

• Lee RJ, Lakkireddy D, Mittal S, Ellis C, Connor JT, Saville BR, Wilber D. Percutaneous alternative to the Maze procedure for the treatment of persistent or long-standing persistent atrial fibrillation (aMAZE trial): Rationale and design. Am Heart J. 2015 Dec;170(6):1184-94. doi: 10.1016/j.ahj.2015.09.019. Epub 2015 Oct 3.

Helpful Links

• aMAZE Trial website

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): April 21, 2021
• Study Completion (ANTICIPATED): March 1, 2022

Study Registration Dates

• First Submitted: July 30, 2015
• First Submitted That Met QC Criteria: July 30, 2015
• First Posted (ESTIMATE): August 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: RS-011