Safety and Efficacy Continued Access Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in Very High Risk Subjects and High Risk Subjects Who Need Aortic Valve Replacement

Severe Aortic Stenosis Clinical Trial

Official title:

Medtronic CoreValve® Continued Access Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01531374
• Other study ID #: 10037989DOC REV 1C
• Status: Completed
• Phase: N/A
• Start date: February 21, 2012
• Est. completion date: November 18, 2019

Study information

• Verified date: October 2022
• Source: Medtronic Cardiovascular
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety and efficacy of the Medtronic CoreValve® System in the treatment of symptomatic severe aortic stenosis in subjects who have a predicted very high risk and high risk for aortic valve surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2777
• Est. completion date: November 18, 2019
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. High Risk: Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that predicted risk of operative mortality is =15% (and predicted operative mortality or serious, irreversible morbidity risk of < 50%) at 30 days.

OR

Extreme Risk: Subject must have co-morbidities such that one cardiologist and two cardiac surgeons agree that medical factors preclude operation, based on a conclusion that the probability of death or serious morbidity exceeds the probability of meaningful improvement. Specifically, the predicted operative risk of death or serious, irreversible morbidity is = 50% at 30 days.

2. Subject has senile degenerative aortic valve stenosis with:

• Mean gradient > 40 mmHg, or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram, or simultaneous pressure recordings at cardiac catheterization (either resting or dobutamine stress), AND

• An initial aortic valve area of = 0.8 cm2 (or aortic valve area index = 0.5 cm2/m2) by resting echocardiogram or simultaneous pressure recordings at cardiac catheterization

3. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater.

4. The subject or the subject's legal representative has been informed of the nature of the trial, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site.

5. The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria:

Clinical

1. Evidence of an acute myocardial infarction = 30 days before the intended treatment.

2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure including bare metal and drug eluting stents.

3. Blood dyscrasias as defined: leukopenia (WBC < 1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.

4. Untreated clinically significant coronary artery disease requiring revascularization.

5. Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.

6. Need for emergency surgery for any reason.

7. Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) < 20% as measured by resting echocardiogram.

8. Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA).

9. End stage renal disease requiring chronic dialysis or creatinine clearance < 20 cc/min.

10. Active GI bleeding that would preclude anticoagulation.

11. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

• Aspirin

• Heparin (HIT/HITTS) and bivalirudin

• Nitinol (titanium or nickel)

• Ticlopidine and clopidogrel

• Contrast media

12. Ongoing sepsis, including active endocarditis.

13. Subject refuses a blood transfusion.

14. Life expectancy < 12 months due to associated non-cardiac co-morbid conditions.

15. Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent.

16. Severe dementia (resulting in either inability to provide informed consent for the trial/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).

17. Currently participating in an investigational drug or another device trial.

18. Symptomatic carotid or vertebral artery disease.

Anatomical

19. High Risk:Native aortic annulus size < 20 mm or > 29 mm per the baseline diagnostic imaging (until 23mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort)

OR

Extreme Risk: Native aortic annulus size < 18 mm or > 29 mm per the baseline diagnostic imaging. (High risk and extreme risk upon 23mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort)

20. Pre-existing prosthetic heart valve any position.

21. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation (3-4+)).

22. Moderate to severe (3-4+) or severe (4+) mitral or severe (4+) tricuspid regurgitation.

23. Moderate to severe mitral stenosis.

24. Hypertrophic obstructive cardiomyopathy.

25. Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation.

26. Severe basal septal hypertrophy with an outflow gradient.

27. Aortic root angulation (angle between plane of aortic valve annulus and horizontal plane/vertebrae) > 70° (for femoral and left subclavian/axillary access) and > 30° (for right subclavian/axillary access).

28. Ascending aorta diameter >43 mm if the aortic annulus diameter is 23-29 mm; ascending aortic diameter > 40 mm if the aortic annulus diameter is 20-23 mm; or an ascending aorta diameter > 34 mm if the aortic annulus diameter is 18-20 mm (Extreme Risk only until 23 mm valve enrollment completion/closure in the CoreValve® US Pivotal Trial-High Risk Cohort).

29. Congenital bicuspid or unicuspid valve verified by echocardiography.

30. Sinus of valsalva anatomy that would prevent adequate coronary perfusion.

Vascular

31. Transarterial access not able to accommodate an 18Fr sheath.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Severe Aortic Stenosis

Intervention

Device:
• Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Locations

Country	Name	City	State
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	Piedmont Heart Institute	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	University Hospitals - Case Medical Center	Cleveland	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Ohio State University Medical Center - The Richard M. Ross Heart Hospital	Columbus	Ohio
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Iowa Heart Center	Des Moines	Iowa
United States	Detroit Medical Center Cardiovascular Institute	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Spectrum Health Hospitals	Grand Rapids	Michigan
United States	Pinnacle Health	Harrisburg	Pennsylvania
United States	Hartford Hospital	Hartford	Connecticut
United States	Cardiovascular Institute of the South/Terrebonne General	Houma	Louisiana
United States	Texas Heart Institute at St. Luke's Episcopal Hospital	Houston	Texas
United States	The Methodist Hospital - The Methodist DeBakey Heart & Vascular Center	Houston	Texas
United States	St. Vincent Heart Center of Indiana	Indianapolis	Indiana
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Kaiser Permanente - Los Angeles Medical Center	Los Angeles	California
United States	University of Southern California University Hospital	Los Angeles	California
United States	North Shore University Hospital/ Long Island Jewish Hospital	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami Health System / Jackson Memorial Hospital	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	St. Luke's Medical Center - Aurora Health Care	Milwaukee	Wisconsin
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	El Camino Hospital	Mountain View	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Lenox Hill Hospital	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	The Mount Sinai Medical Center	New York	New York
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Banner Good Samaritan	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	St. Francis Hospital	Roslyn	New York
United States	Providence Sacred Heart Medical Center	Spokane	Washington
United States	Washington Hospital Center / Georgetown Hospital	Washington	District of Columbia
United States	Wake Forest University - Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiovascular

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality	All-cause Death or Major Stroke (Extreme Risk- Medtronic CoreValve® System); All-cause Mortality (High Risk Surgical- Medtronic CoreValve® System vs. Surgical Valve)	1 year
Secondary	Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)	MACCE is defined as a composite of: All-Cause Death; Myocardial Infarction (MI); All Stroke; Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	The Occurrence of Individual MACCE Components	Individual MACCE Components Include: All Cause Mortality; MI; All stroke; Reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Major Adverse Events (MAEs)	MAEs Include: MACCE; Acute Kidney Injury; Cardiac Tamponade; Prosthetic Valve Dysfunction; Cardiogenic Shock; Valve Endocarditis; Life-Threatening, Disabling or Major Bleeding; Major Vascular Complication; Cardiac Perforation; Device Migration/Valve Embolism	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Conduction Disturbance Requiring Permanent Pacemaker Implantation		30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Change From Baseline in NYHA Class	Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.; NYHA Classification: Class I: Subjects with cardiac disease but without resulting limitations of physical activity.; Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.; Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.; Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.	Baseline to 30 days, baseline to 6 months, baseline to 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Change From Baseline in Distance Walked During 6-Minute Walk Test (6MWT)	Change in distance walked during 6MWT from baseline	Baseline to 30 days, baseline to 1 year
Secondary	Ratio of Days Alive Out of Hospital at 365 Days Post Procedure Versus Total Days Alive		1 year
Secondary	Quality of Life (QoL) Change	QoL summary score change from baseline using the following measures: Kansas City Cardiomyopathy Questionnaire (KCCQ): Quantifies physical function, symptoms, social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.; 12 Item Short Form Health Survey (SF-12): Measures functional health and well-being. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.; European QoL (EQ-5D): Measures 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that can be converted to utilities using an algorithm. Utilities range from 0 to 1, with 1 representing perfect health, and 0 corresponding to the worst imaginable health state.	30 day, 6 month, 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Echocardiographic Assessment of Valve Performance	Using the following measure: • Effective Orifice Area (EOA) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Echocardiographic Assessment of Valve Performance	Using the following measure: • Transvalvular Mean Gradient analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Echocardiographic Assessment of Valve Performance	Using the following measure: - Degree of Aortic Valve Regurgitation (Transvalvular and Paravalvular) analyzed overall per Extreme Risk or High Risk. Iliofemoral access and non-iliofemoral access are not reported separate because this is a valve performance measurement.	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Aortic Valve Hospitalizations		30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Cardiovascular Deaths and Valve-Related Deaths		30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Strokes and Transient Ischemic Attacks (TIAs)	Strokes (of any severity) and TIAs	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.
Secondary	Index Procedure Related MAEs		Procedure
Secondary	Length of Index Procedure Hospital Stay		Number of days from admission to discharge
Secondary	Device Success	Defined as: Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system,; Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function),; Intended performance of the prosthetic valve (aortic valve area > 1.2 cm2 for 26, 29 and 31mm valves, = 0.9 cm2 for 23mm valve (by echocardiography using the continuity equation) and mean aortic valve gradient < 20 mmHg or peak velocity < 3 m/sec, without moderate or severe prosthetic valve aortic regurgitation); Only one valve implanted in the proper anatomical location	Number of days from admission to discharge
Secondary	Procedural Success	Defined as device success and absence of in-hospital MACCE.	Number of days from admission to discharge
Secondary	Prosthetic Valve Dysfunction (PVD)	PVD was defined according to VARC using the site reported echocardiography assessments including aortic regurgitation (AR) and aortic stenosis (AS) evaluations. Total AR reported as moderate or severe was considered PVD. AS was defined as significant stenosis and considered PVD if one of the following was met: Peak velocity >4 m/s; Mean gradient >35 mmHg; EOA < 0.8 cm2; TVIV1 / TVIV2 < 0.25	30 day, 6 months, and 1 year. The 2-5 year outcome data will be reported once data set is complete.