Surgical Implantation of TRAnscatheter vaLve in Native Mitral Annular Calcification (SITRAL) Study (SITRAL)

The purpose of this study is to establish the safety and feasibility of the Edwards SAPIEN 3 valve in subjects with mitral annular calcification (MAC) associated with mitral stenosis (MS) and/or mitral regurgitation who are at high-risk for mitral valve surgery or deemed inoperable due to the extent of calcification.

Study Overview

• Status: Completed
• Conditions: Mitral Annular Calcification
• Intervention / Treatment: Device: Mitral Valve Replacement (MVR) with Sapien3

Detailed Description

Technical Success:

Alive, with

• Successful access, delivery and retrieval of the device delivery system, and
• Deployment and correct positioning (including repositioning/recapture if needed) of the single intended device, and
• No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure

Device Success:

Alive and stroke free, with

• Original intended device in place, and
• No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/Operating Room(OR)), and

• Intended performance of the device:

  • Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and
  • Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = Mitral Valve Area (MVA) < 1.5cm2 and Mitral Valve (MV) gradient > 5mmHg, Insufficiency = Mitral Regurgitation (MR) >1+), and
  • Absence of para-device complications (e.g., Paravalvular Leak (PVL) > mild, need for a Permanent Pacemaker (PPM), erosion, Annular rupture or Aortic Valve (AV) Groove disruption, Left Ventricular Outflow Tract (LVOT) gradient increase > 10mmHg)

Procedural Success:

Device success, and

• No device or procedure related Serious Adverse Events (SAEs) (Life threatening bleed; major vascular or cardiac structural complications requiring unplanned reintervention or surgery; stage 2 or 3 Acute Kidney Injury (includes new dialysis); Myocardial Infarction (MI) or need for percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG); severe heart failure (HF) or hypotension requiring intravenous (IV) inotrope, ultrafiltration or mechanical circulatory support; prolonged intubation ( > 48 hours)

6.2 Secondary objective(s)

Device Success (at 6 months and 1 year)

• Subject success 1 year

Device Success:

Alive and stroke free, with

• Original intended device in place, and
• No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/Operating Room (OR)), and

• Intended performance of the device:

  • Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, and
  • Hemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = MVA < 1.5cm2 and MV gradient > 5mmHg, Insufficiency = MR >1+), and
  • Absence of para-device complications (e.g., PVL > mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase > 10mmHg)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent Heart Center
  • Maryland
    • Baltimore, Maryland, United States
      • MHRI Maryland
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Institute for Medical Research
  • Texas
    • Houston, Texas, United States
      • Baylor College of Medicine
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has severe native mitral annular calcification associated with mitral stenosis and/or regurgitation. Qualifying echo must be within 60 days of the date of the procedure.
• Subject has a clinical indication for mitral valve replacement, as demonstrated by reported New York Heart Association (NYHA) Functional Class II or greater.
• The subject is at least 22 years old.
• The Heart Team agrees that the subject is high risk or inoperable for surgical mitral valve repair or replacement (MVR), based on a conclusion that the probability of death or serious, irreversible morbidity exceeds the probability of meaningful improvement. The following concomitant procedures, are allowed: Maze, Tricuspid Valve Procedures (TVP), and Atrial Fibrillation (AF) ablation, coronary artery bypass grafting and septal myectomy.
• The study subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
• The study subject agrees to comply with all required post-procedure follow-up visits

Exclusion Criteria:

• Evidence of an acute myocardial infarction (MI) ≤ 30 days before the intended treatment [defined as: Q wave MI, or non-Q wave MI with total creatine kinase (CK) elevation of creatine kinase-myocardial band (CK-MB) ≥ twice normal in the presence of myocardial band (MB) elevation and/or troponin level elevation (WHO definition)].
• Any therapeutic invasive cardiac procedure resulting in a permanent implant that is performed within 30 days of the index procedure (unless part of planned strategy for treatment of concomitant coronary artery disease).
• Leukopenia (white blood cell count < 2000 cell/mL), acute anemia (hemoglobin < 8 g/dL), or thrombocytopenia (platelet count < 50,000 cell/mL).
• Hemodynamic or respiratory instability requiring vasoactive medications, mechanical ventilation at time of procedure.
• Need for emergency surgery for any reason.
• Severe left ventricular dysfunction with Left Ventricular Ejection Fraction (LVEF) < 30%.
• Severe right ventricular dysfunction
• Pregnancy, lactation, or planning to become pregnant
• Echocardiographic evidence of left ventricular mass, thrombus, or concerns of active infective endocarditis.
• Active upper gastrointestinal (GI) bleeding within 3 months prior to procedure without treatment or 30 days prior to procedure with definitive treatment.
• A known contraindication or hypersensitivity to all anticoagulation regimens, or inability to be maintained on oral anticoagulant following the study procedure.
• End stage renal disease requiring dialysis
• Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic attack (TIA) within 30 days of the procedure.
• Estimated life expectancy < 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mitral Valve Replacement (MVR) with Sapien3; subjects with surgical MVR with Sapien3	Device: Mitral Valve Replacement (MVR) with Sapien3; subjects with surgical MVR with Sapien3; Other Names: MVR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedural Success	Procedural Success is defined as: Device success, and; No device or procedure related serious adverse events (SAEs) (Life threatening bleed; major vascular or cardiac structural complications requiring unplanned reintervention or surgery; stage 2 or 3 acute kidney injury (AKI) (includes new dialysis); myocardial infarction (MI) or need for percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG); severe heart failure (HF) or hypotension requiring intravenous (IV) inotrope, ultrafiltration or mechanical circulatory support; prolonged intubation ( > 48 hours)	30 days
Technical Success	Technical Success is defined as: Alive, with; Successful access, delivery and retrieval of the device delivery system, and; Deployment and correct positioning (including repositioning/recapture if needed) of the single intended device, and; No need for additional unplanned or emergency surgery or re-intervention related to the device or access procedure	Procedure Stop Time
Device Success	Device Success is defined as: Alive and stroke free, with; Original intended device in place, and; No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/operating room (OR)), and; Intended performance of the device:Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, andHemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = mitral valve area (MVA) < 1.5cm2 and mitral valve (MV) gradient > 5mmHg, Insufficiency = mitral regurgitation (MR) >1+), andAbsence of para-device complications (e.g., paravalvular leak (PVL) > mild, need for a permanent pacemaker (PPM), erosion, Annular rupture or aortic valve (AV) Groove disruption, left ventricular outflow tract (LVOT) gradient increase > 10mmHg)	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Success	Device Success is defined as: Alive and stroke free, with; Original intended device in place, and; No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/OR), and; Intended performance of the device:Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, andHemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = MVA < 1.5cm2 and MV gradient > 5mmHg, Insufficiency = MR >1+), andAbsence of para-device complications (e.g., PVL > mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase > 10mmHg)	1 year
Device Success	Device Success is defined as: Alive and stroke free, with; Original intended device in place, and; No additional surgical or interventional procedures related to access or the device since completion of the original procedure (i.e., exit from the cath lab/operating room (OR)), and; Intended performance of the device:Structural performance: No migration, embolization, detachment, fracture, hemolysis, thrombosis (including reduced leaflet motion) or endocarditis, etc, andHemodynamic performance: Maintenance of relief of stenosis or insufficiency without producing the opposite (Stenosis = MVA < 1.5cm2 and MV gradient > 5mmHg, Insufficiency = MR >1+), andAbsence of para-device complications (e.g., PVL > mild, need for a PPM, erosion, Annular rupture or AV Groove disruption, LVOT gradient increase > 10mmHg)	6 months
Subject Success	Subject Success is defined as: All of the following must be present: I. Device success (either optimal or acceptable), and II. Patient returned to the pre-procedural setting: and III. No rehospitalizations or reinterventions for the underlying condition (e.g., mitral regurgitation, heart failure); and IV. Improvement from baseline in symptoms (e.g., NYHA improvement by > or = 1 functional class); and V. Improvement from baseline in functional status (e.g., 6-min walk test improvement by > or = 50 m); and VI. Improvement from baseline in quality-of-life (e.g., Kansas City Cardiomyopathy Questionnaire improvement by > or = 10)	1 year

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Collaborators: Edwards Lifesciences
• Investigators: Principal Investigator: Robert Smith, MD, Baylor Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2016
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: May 4, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimated): July 12, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: mitral valve regurgitation; mitral valve stenosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Calcium Metabolism Disorders; Calcinosis
• Other Study ID Numbers: 016-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is currently no plan to share individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes