Feasibility of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic, Severe Aortic Stenosis

May 14, 2024 updated by: Medstar Health Research Institute
To assess the safety and feasibility of Transcatheter Aortic Valve Replacement (TAVR) with commercially available bioprostheses in patients with severe, symptomatic aortic stenosis (AS) who are low-risk (STS score ≤3%) for surgical aortic valve replacement (SAVR).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Trial Objectives: To assess the safety and feasibility of Transcatheter Aortic Valve Replacement (TAVR) with commercially available bioprostheses in patients with severe, symptomatic aortic stenosis (AS) who are low-risk (STS score ≤3%) for surgical aortic valve replacement (SAVR).

Methodology: This is a multicenter, prospective trial of TAVR in low-risk patients at up to twelve sites in the United States. The trial will have three arms. The first will comprise 200 patients undergoing transfemoral TAVR. The second arm will comprise200 closely matched historical controls who underwent isolated bioprosthetic SAVR.

Historical controls will be selected from among patients at the same site who have undergone isolated bioprosthetic SAVR within the previous 36 months. TAVR patients will then be matched to SAVR patients using STS database variables to perform propensity matching, including (but not limited to) age, gender, race, ethnicity, STS score, and valve prosthesis size. Once the historical matched controls are identified, detailed chart review will abstract in-hospital and 30-day outcomes for the SAVR cohort.

The third arm of the trial will comprise a registry of TAVR in up to 100 low-risk patients with bicuspid aortic valve. The results from the registry arm will be analyzed independently.

Primary Efficacy Endpoint: All-cause mortality at 30 days following transfemoral TAVR vs. bioprosthetic SAVR.

Primary Safety Endpoint: Defined as the composite of major adverse events at 30 days:

a. all-cause mortality c. spontaneous myocardial infarction (MI) d. reintervention: defined as any cardiac surgery or percutaneous reintervention that repairs, alters, or replaces a previously implanted aortic valve e. VARC life-threatening bleeding f. Increase in serum creatinine to ≥300% (>3x increase compared to baseline) OR serum creatinine ≥4.0 mg/dL with an acute increase ≥0.5 mg/dL OR new requirement for dialysis g. coronary artery obstruction requiring percutaneous or surgical intervention h. VARC major vascular complication i. cardiac tamponade j. cardiac perforation k. pericarditis l. mediastinitis m. hemolysis n. infective endocarditis o. moderate or severe aortic insufficiency p. significant aortic stenosis q. permanent pacemaker implantation r. new-onset atrial fibrillation

Secondary Endpoints (TAVR Cohort):

  1. Major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days, 6 months, 12 months, and 2, 3, 4 and 5 years, defined as the composite of:

    1. all-cause mortality
    2. stroke
    3. spontaneous MI
    4. reintervention
  2. The occurrence of the individual components of MACCE at 30 days, 6 months, 12 months, and 2, 3, 4, and 5 years (including stoke).
  3. The composite of major adverse device events post-procedure, and at 6 months, 1 year, and 2, 3, 4, 5 years
  4. VARC major vascular complications, at 30 days and 1 year
  5. VARC life-threatening or disabling bleeding, at 30 days and 1 year

  6. Technical success upon exit from the operating room or catheterization laboratory, defined as all of the following:

    1. alive
    2. successful access, delivery, and retrieval of the device and/or delivery system
    3. correct positioning and successful deployment of the valve
    4. no need for unplanned or emergency surgery or reintervention related to the device or access procedure, including reinstitution of cardiopulmonary bypass post-weaning for SAVR patients

  7. Device success at 30 days and 1 year, defined as all of the following:

    1. absence of procedural mortality
    2. correct positioning of a single prosthetic heart valve in the proper anatomical location
    3. device performing as intended:

1. No migration, erosion, embolization, detachment, fracture, hemolysis requiring transfusion, thrombosis, or endocarditis 2. Intended performance of the heart valve: no prosthesis-patient mismatch, mean aortic valve gradient <20 mm Hg OR peak velocity <3 m/s, AND no moderate or severe bioprosthetic valve regurgitation 8. Procedural success at 30 days, defined as device success AND no major adverse device events 9. Bioprosthetic valve regurgitation, defined as either moderate or severe aortic regurgitation OR moderate or severe paravalvular leak, at hospital discharge, 12 months, and 2, 3, 4, and 5 years 10. Incidence of new-onset atrial fibrillation at hospital discharge, and at 30 days, 12 months, and 2, 3, 4, and 5 years.

11. Conduction disturbance requiring permanent pacemaker implantation at hospital discharge, 12 months, and 2, 3, 4, and 5 years.

12. Change in NYHA class from baseline to 30 days, baseline to 6 months, baseline to 12 months, and baseline to 2-5 years.

13. Change in distance walked during 6-minute walk test from baseline to 12 months.

14. Change in responses to the short form Kansas City Cardiomyopathy Questionnaire (KCCQ-12) from baseline to 12 months.

15. Echocardiographic assessment of the bioprosthetic valve post-procedure, at 12 months, and at years 2-5, including (but not limited to):

a. aortic valve mean gradient, maximum gradient, and peak velocity b. calculated aortic valve area c. degree of bioprosthetic valve regurgitation 16. Assessment for subclinical leaflet thrombosis with multislice computed tomography, or transesophageal echocardiography if GFR <50 mL/min/m2, at 1 to 2 months.

17. Individual patient level Success all of the following and device success:

  1. No re-hospitalizations or re-interventions for the underlying condition (e.g., HF)
  2. Return to prior living arrangement (or equivalent)
  3. Improvement vs. baseline in symptoms (NYHA Class decrease ≥ 1)
  4. Improvement vs. baseline in functional status (6MWT increase ≥ 50 meters)
  5. Improvement vs. baseline in QoL (KCCQ increase ≥ 10)

Number of Trial Sites: 12

Sample Size: 200 consecutive patients and 200 historical controls, and an additional 100 (up to) patients with bicuspid aortic valve

Patient Population: Patients with severe, symptomatic AS who are determined by the Heart Team to be at low surgical risk (STS score ≤3%).

Study Type

Interventional

Enrollment (Actual)

277

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95816
        • Sutter Health System
      • San Diego, California, United States, 92121
        • Foundation for Cardiovascular Medicine
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Medstar Washington Hospital Center
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Wellstar Kennestone Hospital
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • New Jersey
      • Ridgewood, New Jersey, United States, 07450
        • The Valley Hospital
    • New York
      • Stony Brook, New York, United States, 11794
        • Stony Brook Hospital
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
        • St. John Health System
    • Rhode Island
      • Providence, Rhode Island, United States, 02906
        • Miriam Hospital
    • Virginia
      • Richmond, Virginia, United States, 23229
        • Henrico Doctors' Hospital
      • Richmond, Virginia, United States, 23298
        • VCU Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Severe, degenerative AS, defined as:

    1. mean aortic valve gradient ≥40 mm Hg OR Vmax ≥4 m/sec AND
    2. calculated aortic valve area ≤1.0 cm2 OR aortic valve area index ≤0.6 cm2/m2

  2. Symptomatic AS, defined as a history of at least one of the following:

    1. dyspnea that qualifies at New York Heart Association (NYHA) class II or greater
    2. angina pectoris
    3. cardiac syncope
  3. The Heart Team, including at least one cardiothoracic surgeon and one interventional cardiologist, deem the patient to be reasonable for transfemoral TAVR with a commercially available bioprosthetic valve
  4. The Heart Team agrees that the patient is low-risk, quantified by an estimated risk of ≤3% by the calculated STS score for operative mortality at 30 days; AND agrees that SAVR would be an appropriate therapy if offered.
  5. The Heart Team agrees that transfemoral TAVR is anatomically feasible, based upon multislice CT measurements
  6. Procedure status is elective

  7. Expected survival is at least 24 months

    For the bicuspid cohort only:

  8. Aortic Stenosis of a bicuspid aortic valve

Exclusion Criteria:

  1. Concomitant disease of another heart valve or the aorta that requires either transcatheter or surgical intervention
  2. Any condition that is considered a contraindication for placement of a bioprosthetic aortic valve (e.g. patient requires a mechanical aortic valve)
  3. Aortic stenosis secondary to a bicuspid aortic valve (except for the bicuspid valve cohort)
  4. Prior bioprosthetic surgical aortic valve replacement
  5. Mechanical heart valve in another position
  6. End-stage renal disease requiring hemodialysis or peritoneal dialysis, or a creatinine clearance <20 cc/min
  7. Left ventricular ejection fraction <20%
  8. Recent (<6 months) history of stroke or transient ischemic attack
  9. Symptomatic carotid or vertebral artery disease, or recent (<6 weeks) surgical or endovascular treatment of carotid stenosis
  10. Any contraindication to oral antiplatelet or anticoagulation therapy following the procedure, including recent or ongoing bleeding, or HASBLED score >3
  11. Severe coronary artery disease that is unrevascularized
  12. Recent (<30 days) acute myocardial infarction
  13. Patient cannot undergo transfemoral TAVR for anatomic reasons (as determined by supplemental imaging studies); this would include inadequate size of iliofemoral access vessels or an aortic annulus size that is not accommodated by the commercially available valves

  14. Any comorbidity not captured by the STS score that would make SAVR high risk, as determined by a cardiothoracic surgeon who is a member of the heart team; this includes:

    1. porcelain or severely atherosclerotic aorta
    2. frailty
    3. hostile chest
    4. IMA or other conduit either crosses midline of sternum or is adherent to sternum
    5. severe pulmonary hypertension (PA systolic pressure > 2/3 of systemic pressure)
    6. severe right ventricular dysfunction
  15. Ongoing sepsis or infective endocarditis
  16. Recent (<30 days) or ongoing bleeding that would preclude treatment with anticoagulant or antiplatelet therapy, including recent gastrointestinal bleeding
  17. Uncontrolled atrial fibrillation (resting heart rate >120 beats per minute)
  18. Severe chronic obstructive pulmonary disease, as demonstrated by forced expiratory volume (FEV1) <750 cc
  19. Liver failure with Childs class C or D
  20. Pre-procedure shock, inotropes, mechanical assist device, or cardiac arrest
  21. Pregnancy or intent to become pregnant prior to completion of all protocol follow-up procedures
  22. Known allergy to warfarin or aspirin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Prospective TAVR Arm
200 patients prospectively undergoing transfemoral TAVR
Device: Transfemoral TAVR
Other Names:
  • Transcatheter aortic valve replacement
Other: Historical SAVR Controls
Historical controls will be selected from among patients at the same site who have undergone isolated bioprosthetic SAVR within the previous 36 months. TAVR patients will then be matched to SAVR patients using STS database variables to perform propensity matching, including (but not limited to) age, gender, race, ethnicity, STS score, and valve prosthesis size.
Device: SAVR
Other Names:
  • Surgical Aortic Valve Replacement
Other: Low-Risk TAVR with Bicuspid Aortic Valve
The third arm of the trial will comprise a registry of TAVR in up to 100 low-risk patients with bicuspid aortic valve. The results from the registry arm will be analyzed independently.
Device: Transfemoral TAVR
Other Names:
  • Transcatheter aortic valve replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Vascular Complications
Time Frame: 30 days
30 days
All Cause Mortality
Time Frame: 30 days
30 days
Hospitalizations for valve-related symptoms or worsening congestive heart failure
Time Frame: 30 days
30 days
All-cause mortality at 30 days following transfemoral TACR vs. bioprosthetic SAVR
Time Frame: 30 days following transfemoral TAVR vs. bioprosthetic SAVR
All-cause mortality at 30 days following transfemoral TACR vs. bioprosthetic SAVR
30 days following transfemoral TAVR vs. bioprosthetic SAVR
Composite of major adverse events at 30 days
Time Frame: 30 days

Composite of major adverse events at 30 days

  1. all-cause mortality
  2. stroke
  3. spontaneous myocardial infarction (MI)
  4. reintervention: defined as any cardiac surgery or percutaneous reintervention that repairs, alters, or replaces a previously implanted aortic valve
  5. VARC life-threatening bleeding
  6. Increase in serum creatinine to ≥300% (>3x increase compared to baseline) OR serum creatinine ≥4.0 mg/dL with an acute increase ≥0.5 mg/dL OR new requirement for dialysis
  7. coronary artery obstruction requiring percutaneous or surgical intervention
  8. VARC major vascular complication
  9. cardiac tamponade
  10. cardiac perforation
  11. pericarditis
  12. mediastinitis
  13. hemolysis
  14. infective endocarditis
  15. moderate or severe aortic insufficiency
  16. significant aortic stenosis
  17. permanent pacemaker implantation
30 days
All Stroke (disabling and non-disabling, ischemic and hemorrhagic
Time Frame: 30 Days
30 Days
Life Threatening and Major Bleeding
Time Frame: 30 days
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
composite of all-cause mortality, stroke, spontaneous MI, re-intervention
Time Frame: 30 days, 6 months, 12 months, and 2,3,4 and 5 years

composite of:

  1. all-cause mortality
  2. stroke
  3. spontaneous MI
  4. re-intervention 2. The occurrence of the individual components of MACCE at 30 days, 6 months, 12 months, and 2, 3, 4, and 5 years. 3. The composite of major adverse device events post-procedure, and at 6 months, 1 year, and 2, 3, 4, 5 years 4. VARC major vascular complications, at 30 days and 1 year 5. VARC life-threatening or disabling bleeding, at 30 days and 1 year 6. Assessment for subclinical leaflet thrombosis with multislice computed tomography, or transesophageal echocardiography if GFR <50 mL/min/m2, at 1 to 2 months.
30 days, 6 months, 12 months, and 2,3,4 and 5 years
VARC - 2 Device Success
Time Frame: 30 days
Absence of procedural mortality AND Correct positioning of a single prosthetic heart valve into the proper anatomical location AND Intended performance of the prosthetic heart valve (no prosthesis-patient mismatch and mean aortic valve gradient<20 mm Hg or peak velocity<3 m/s, AND no moderate or severe prosthetic valve regurgitation)
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medstar Health Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2016

Primary Completion (Actual)

January 1, 2023

Study Completion (Actual)

January 1, 2023

Study Registration Dates

First Submitted

December 4, 2015

First Submitted That Met QC Criteria

December 9, 2015

First Posted (Estimated)

December 11, 2015

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 14, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Low Risk TAVR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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