Clinical trial NCT02513797: aMAZE Study: LAA Ligation Adjunctive to PVI for Persistent or Longstanding Persistent Atrial Fibrillation
Official title: Left Atrial Appendage Ligation With the LARIAT™ Suture Delivery System as Adjunctive Therapy to Pulmonary Vein Isolation for Persistent or Longstanding Persistent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Atrial Fibrillation
Lead sponsor: AtriCure, Inc.
Sponsor class: INDUSTRY
First posted: 2015-08-03
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Freedom from episodes of atrial fibrillation > 30 seconds at 12 months post index pulmonary vein isolation
timeFrame: 12 months following Pulmonary Vein Isolation catheter ablation procedure
Secondary outcomes:
measure: Freedom from any atrial fibrillation/atrial tachycardia/atrial flutter recurrence defined as any episode > 30 seconds with or without AAD
timeFrame: Following the 90 day blanking period through 12 months post-index pulmonary vein isolation
measure: Composite endpoint of stroke of any cause and systemic embolism as adjudicated by the clinical events committee
timeFrame: 12 months following index pulmonary vein isolation
Other outcomes:
measure: LARIAT Technical Success
timeFrame: Immediately post-LARIAT ligation (acute) and at 12 months following index pulmonary vein isolation
Locations:
city: Phoenix
country: United States
facility: Arizona Arrhythmia Research Center
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: St. Vincent's HealthCare
state: Florida
city: Athens
country: United States
facility: Piedmont Athens Regional Cardiology
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Honolulu
country: United States
facility: The Queen's Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University / Bluhm Cardiovascular Institute
state: Illinois
city: Maywood
country: United States
facility: Loyola University Center for Heart and Vascular Medicine
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Winfield
country: United States
facility: Northwestern Medicine Central DuPage Hospital
state: Illinois
city: Munster
country: United States
facility: Community Hospital
state: Indiana
city: West Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cardiac Arrhythmia Research
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Houma
country: United States
facility: Cardiovascular Institute of the South Clinical Research Corporation
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Marquette
country: United States
facility: UP Health System- Marquette
state: Michigan
city: Kansas City
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Las Vegas
country: United States
facility: DaVita Medical Group
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Ridgewood
country: United States
facility: The Valley Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio Health Research Institute
state: Ohio
city: Medford
country: United States
facility: Southern Oregon Cardiology
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Bryn Mawr
country: United States
facility: Bryn Mawr Medical Specialists Association / Bryn Mawr Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Trident Medical Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research Foundation
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Houston
country: United States
facility: Baylor - St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Plano
country: United States
facility: Baylor Plano Scott & White Research Institute Heart Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Tyler
country: United States
facility: Christus Trinity Mother Frances Health System
state: Texas
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
Study officials:
affiliation: Loyola University Department of Medicine
name: David J Wilber, MD
role: STUDY_CHAIR
affiliation: Kansas City Cardiac Arrhythmia Research
name: Dhanunjaya Lakkireddy, MD
role: STUDY_CHAIR
References:
citation: 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.