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

• ClinicalTrials.gov Identifier: NCT02628899
• Recruitment Status: Recruiting
• First Posted: December 11, 2015
• Last Update Posted: June 18, 2018
• Sponsor: Medstar Health Research Institute
• Information provided by (Responsible Party): Medstar Health Research Institute

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Aortic Stenosis	Device: Transfemoral TAVR; Device: SAVR	Not Applicable

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: January 2016
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: January 2023

Arms and Interventions

Arm	Intervention/treatment
Prospective TAVR Arm; 200 patients prospectively undergoing transfemoral TAVR	Device: Transfemoral TAVR; Other Name: Transcatheter aortic valve replacement
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 Name: Surgical Aortic Valve Replacement
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 Name: Transcatheter aortic valve replacement

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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
3. All Cause Mortality [ Time Frame: 30 days ]
4. All Stroke (disabling and non-disabling, ischemic and hemorrhagic [ Time Frame: 30 Days ]
5. Life Threatening and Major Bleeding [ Time Frame: 30 days ]
6. Major Vascular Complications [ Time Frame: 30 days ]
7. Hospitalizations for valve-related symptoms or worsening congestive heart failure [ Time Frame: 30 days ]

Secondary Outcome Measures :

1. 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.
2. 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)

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Sutter Health System; Recruiting

Sacramento, California, United States, 95816

Contact: Wynell Richardson 916-887-4172 MelvinW@sutterhealth.org

Principal Investigator: David Roberts, MD

Sub-Investigator: Michael Ingram, MD

Foundation for Cardiovascular Medicine; Recruiting

San Diego, California, United States, 92121

Contact: Diane Wilkerson, RN 858-625-4488 dwilkerson@fcvmed.org

Principal Investigator: Maurice Buchbinder, MD

United States, District of Columbia

MedStar Washington Hospital Center; Recruiting

Washington, District of Columbia, United States, 20010

Contact: Roshni S Bastian, MPH 202-877-7752 roshni.s.bastian@medstar.net

Principal Investigator: Ron Waksman, MD

United States, Georgia

WellStar Kennestone Hospital; Recruiting

Marietta, Georgia, United States, 30060

Contact: Barbara Ann Foster, RN 770-793-5974 Barbara.A.Foster@wellstar.org

Principal Investigator: Amar Patel, MD

Sub-Investigator: William Cooper, MD

United States, Maine

Maine Medical Center; Recruiting

Portland, Maine, United States, 04102

Contact: Susan Bosworth-Farrell, RN 207-662-2687 SABosworth@mmc.org

Contact: Joanne Burgess, RN 207-662-6317 BURGEJS@mmc.org

Principal Investigator: David Butzel, MD

United States, New Jersey

The Valley Hospital; Recruiting

Ridgewood, New Jersey, United States, 07450

Contact: Kimberly Michel, RN 201-447-8453 kmichel@valleyhealth.com

Principal Investigator: John A Goncalves, MD

Sub-Investigator: Sean R Wilson, MD

Sub-Investigator: Thomas P Cocke, MD

United States, New York

Stony Brook Hospital; Recruiting

Stony Brook, New York, United States, 11794

Contact: Ruth Stein, RN 631-444-3309 ruth.stein@stonybrookmedicine.edu

Contact: Samantha Maier, SN 631-444-3309 Samantha.Maier@stonybrook.edu

Principal Investigator: Luis Gruberg, MD

Principal Investigator: Thomas Bilfinger, MD

Sub-Investigator: Giridhar Korlipara, MD

Sub-Investigator: Puja Parikh, MD

Sub-Investigator: Henry Tannous, MD

Sub-Investigator: Jonathan Weinstein, MD

United States, Oklahoma

St. John Health System; Recruiting

Tulsa, Oklahoma, United States, 74104

Contact: Grace Aquino, RN 918-744-3426 Grace.Aquino@ascension.org

Contact: Christopher O Fergus, RN 918-744-3426 Christopher.Fergus@ascension.org

Principal Investigator: Nicholas Hanna, MD

Sub-Investigator: Robert Garrett, MD

United States, Rhode Island

Miriam Hospital; Recruiting

Providence, Rhode Island, United States, 02906

Contact: Elizabeth Coccio 401-793-5554

Principal Investigator: Paul Gordon, MD

United States, Virginia

Henrico Doctors' Hospital; Recruiting

Richmond, Virginia, United States, 23229

Contact: Kyle Narron 804-287-4312 Kyle.Narron@SarahCannon.com

Principal Investigator: Robert Levitt, MD

Principal Investigator: Chiown Hahn, MD

VCU Medical Center; Recruiting

Richmond, Virginia, United States, 23298

Contact: Melissa Sears, RN 804-828-1601 melissa.sears@vcuhealth.org

Principal Investigator: Zachary Gertz, MD

Sub-Investigator: Mohammed Quader, MD

Sponsors and Collaborators

Medstar Health Research Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Waksman R, Rogers T, Torguson R, Gordon P, Ehsan A, Wilson SR, Goncalves J, Levitt R, Hahn C, Parikh P, Bilfinger T, Butzel D, Buchanan S, Hanna N, Garrett R, Asch F, Weissman G, Ben-Dor I, Shults C, Bastian R, Craig PE, Garcia-Garcia HM, Kolm P, Zou Q, Satler LF, Corso PJ. Transcatheter Aortic Valve Replacement in Low-Risk Patients With Symptomatic Severe Aortic Stenosis. J Am Coll Cardiol. 2018 Oct 30;72(18):2095-2105. doi: 10.1016/j.jacc.2018.08.1033. Epub 2018 Aug 28.

• Responsible Party: Medstar Health Research Institute
• ClinicalTrials.gov Identifier: NCT02628899 History of Changes
• Other Study ID Numbers: Low Risk TAVR
• First Posted: December 11, 2015
• Last Update Posted: June 18, 2018
• Last Verified: June 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: No
• Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:

Aortic Valve Stenosis; Constriction, Pathologic; Pathological Conditions, Anatomical; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction