Safety & Efficacy Study of the Medtronic CoreValve® System-Treatment of Symptomatic Severe Aortic Stenosis With Significant Comorbidities in Very High Risk Subjects Who Need Aortic Valve Replacement

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Medtronic Cardiovascular
ClinicalTrials.gov Identifier:
NCT01675440
First received: August 22, 2012
Last updated: April 26, 2016
Last verified: April 2016
  Purpose
To evaluate the safety and efficacy of the Medtronic CoreValve® System for the treatment of symptomatic severe aortic stenosis in subjects with significant comorbidities in whom the risk of surgical aortic valve replacement has a predicted operative mortality or serious, irreversible morbidity risk of ≥50% at 30 days.

Condition Intervention
Severe Aortic Stenosis
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Medtronic CoreValve® U.S. Expanded Use Study

Resource links provided by NLM:


Further study details as provided by Medtronic Cardiovascular:

Primary Outcome Measures:
  • All-cause Mortality or Major stroke [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    All-cause Mortality or Major Stroke


Secondary Outcome Measures:
  • Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) Event Rate [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    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)

  • The Occurrence of individual MACCE Components [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    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)

  • Major Adverse Events (MAEs) [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    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

  • Conduction Disturbance Requiring Permanent Pacemaker Implantation [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    The incidence of conduction disturbance requiring permanent pacemaker implantation

  • Change in NYHA Class [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    Change from baseline (continuous variable). A positive number corresponds to NYHA worsening; a negative number corresponds to NYHA improvement.

  • Change in Distance Walked During 6-minute Walk Test (6MWT) from Baseline [ Time Frame: 30 days and 12 months ] [ Designated as safety issue: Yes ]
    Change in distance walked during 6MWT from baseline

  • Ratio of Days Alive Out of Hospital Versus Total Days Alive [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Quality of Life (QoL) Change from Baseline [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    QoL change from baseline using the following measures: •Kansas City Cardiomyopathy Questionnaire (KCCQ) •SF-12 •EuroQoL

  • Echocardiographic Assessment of Valve Performance [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: No ]
    Using the following measures: • Transvalvular mean gradient • Effective orifice area (EOA) •degree of aortic valve regurgitation

  • Aortic Valve Disease Hospitalization [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    The number of subjects re-hospitalized after the initial procedure

  • Cardiovascular Deaths and Valve-related Deaths [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    The number of cardiovascular deaths and valve-related deaths

  • Strokes [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    The number of subjects with strokes and TIAs

  • Index Procedure Related Major Adverse Events (MAEs) [ Time Frame: Procedure ] [ Designated as safety issue: Yes ]
    Index procedure-related MAE events will be summarized

  • Length of Index Procedure Hospital Stay [ Time Frame: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]
    The length of index procedure hospital stay will be summarized

  • Device Success [ Time Frame: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]
    Defined as: 1) Successful vascular access, delivery and deployment of the device, and successful retrieval of the delivery system, 2) Correct position of the device in the proper anatomical location (placement in the annulus with no impedance on device function), 3) 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) 4) Only one valve implanted in the proper anatomical location. For TAV in SAV subjects, only # 1, 2 and 4 will be used to calculate device success.

  • Procedural Success [ Time Frame: Number of days from admission to discharge ] [ Designated as safety issue: Yes ]
    Defined as device success and absence of in-hospital MACCE

  • Evidence of Prosthetic Valve Dysfunction [ Time Frame: 30 days, 6 months, 12 months and annually thereafter up to 5 years ] [ Designated as safety issue: Yes ]
    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


Enrollment: 782
Study Start Date: August 2012
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Severe (≥3-4+) Mitral Valve Regurgitation
Mitral valve regurgitation ≥3-4+
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Severe (≥3-4+) Tricuspid Valve Regurgitation
Tricuspid valve regurgitation ≥3-4+
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
End Stage Renal Disease (ESRD)
End stage renal disease requiring renal replacement therapy or a creatinine clearance (CRCL) <20 cc/min, but not on dialysis
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Low Gradient Low Output Aortic Stenosis
Low gradient low output aortic stenosis
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
Failed Bioprosthetic Surgical Aortic Valve
Stenosed, insufficient or combined bioprosthetic surgical aortic valve failure
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
2 or More Conditions
2 or more of the listed conditions
Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)

Detailed Description:
The primary objective of the study is to evaluate the safety and effectiveness of the Medtronic CoreValve® System (MCS) in a subset of subjects excluded from the U.S. Extreme Risk Pivotal Trial population due to one or more additional co-morbidities, as measured by a composite of all-cause death or major stroke at 12 months, in the treatment of symptomatic severe aortic stenosis in subjects necessitating aortic valve replacement. Subjects enrolled in this study have a predicted operative mortality or serious, irreversible morbidity risk of ≥50% at 30 days associated with surgical aortic valve replacement.
  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Subjects with symptomatic severe aortic stenosis requiring aortic valve replacement, with predicted operative mortality or serious, irreversible morbidity risk of ≥ 50% at 30 days, and at least one of the following conditions:

  • Severe (≥3-4+) mitral valve regurgitation
  • Severe (≥3-4+) tricuspid valve regurgitation
  • End stage renal disease (ESRD) requiring renal replacement therapy or creatinine clearance <20cc/min, but not requiring renal replacement therapy
  • Low gradient, low output aortic stenosis
  • Failed bioprosthetic surgical aortic valve
  • 2 or more conditions (listed above)
Criteria

Inclusion Criteria:

  • 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.
  • Subjects must meet all of the criteria under at least one of the sub-groups 2a-c:

    a. Senile degenerative aortic valve stenosis and i. At least one of the following co-morbid conditions:

    1. Severe (≥3-4+) mitral valve regurgitation as measured by echocardiography
    2. Severe (≥3-4+) tricuspid valve regurgitation as measured by echocardiography
    3. End-stage renal disease requiring renal replacement therapy (Stage 5 of the KDOQI CKD Classification) or creatinine clearance <20cc/min but not requiring renal replacement therapy

      AND

      ii. mean gradient > 40 mmHg or jet velocity greater than 4.0 m/sec by either resting or dobutamine stress echocardiogram (if the LVEF < 50%), or simultaneous pressure recordings at cardiac catheterization either resting or with dobutamine stress (if the LVEF < 50%) AND iii. 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

      AND/OR

      b. Low gradient, low output aortic stenosis as defined by the presence of all three of the following i. In the presence of LVEF <50%, absence of contractile reserve, a mean gradient <40mmHg AND jet velocity less than 4.0m/sec with dobutamine stress echocardiography or simultaneous pressure recordings at cardiac catheterization OR In the presence of LVEF ≥50%, a mean gradient ≥25mmHg and <40mmHg AND jet velocity less than 4.0 m/sec, by echocardiography or simultaneous pressure recordings at cardiac catheterization AND ii. 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 AND iii. radiographic evidence of severe aortic valve calcification AND/OR c. Failed bioprosthetic surgical aortic valve

  • Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by New York Heart Association (NYHA) Functional Class II or greater.
  • The subject or the subject's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent as approved by the IRB of the respective clinical site.
  • The subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits.

Exclusion Criteria:

Clinical

  • Evidence of an acute myocardial infarction ≤30 days before the MCS TAVI procedure.
  • Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the MCS TAVI procedure
  • Blood dyscrasias as defined: leukopenia (WBC <1000mm3), thrombocytopenia (platelet count <50,000 cells/mm3), history of bleeding diathesis or coagulopathy.
  • Untreated clinically significant coronary artery disease requiring revascularization.
  • Cardiogenic shock manifested by low cardiac output, vasopressor dependence, or mechanical hemodynamic support.
  • Need for emergency surgery for any reason.
  • Severe ventricular dysfunction with left ventricular ejection fraction (LVEF) <20% as measured by resting echocardiogram.
  • Recent (within 6 months) cerebrovascular accident (CVA) or transient ischemic attack (TIA).
  • Active Gastrointestinal (GI) bleeding that would preclude anticoagulation.
  • A known hypersensitivity or contraindication to all anticoagulation/antiplatelet regimens (including ability to be anticoagulated for the index procedure), nitinol, or [allergic] sensitivity to contrast media which cannot be adequately pre-medicated.
  • Ongoing sepsis, including active endocarditis.
  • Subject refuses a blood transfusion.
  • Life expectancy <12 months due to associated non-cardiac co-morbid conditions.
  • Other medical, social, or psychological conditions that in the opinion of an Investigator precludes the subject from appropriate consent.
  • Severe dementia (resulting in either inability to provide informed consent for the study/procedure, prevents independent lifestyle outside of a chronic care facility, or will fundamentally complicate rehabilitation from the procedure or compliance with follow-up visits).
  • Currently participating in an investigational drug or another device study.
  • Symptomatic carotid or vertebral artery disease.

Anatomical

Subject has a:

  • Native aortic annulus size <18 mm or >29 mm per the baseline diagnostic imaging (not applicable for TAV in SAV subjects) OR
  • Surgical bioprosthetic annulus <17mm or >29mm i. Stented SAV per the manufactured labeled inner diameter OR ii. Stentless SAV per the baseline diagnostic imaging
  • Subject has a pre-existing prosthetic heart valve with a rigid support structure in either the mitral or pulmonic position:

    1. that could affect the implantation or function of the study valve OR
    2. the implantation of the study valve could affect the function of the pre-existing prosthetic heart valve
  • Moderate to severe mitral stenosis.
  • Mixed aortic valve disease: aortic stenosis and aortic regurgitation with predominant aortic regurgitation, (AR is moderate-severe to severe (≥3-4+))(except for failed surgical bioprothesis)
  • Hypertrophic obstructive cardiomyopathy.
  • Echocardiographic evidence of new or untreated intracardiac mass, thrombus or vegetation.
  • Severe basal septal hypertrophy with an outflow gradient.
  • 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).
  • Ascending aorta that exceeds the maximum diameter for any given native or surgical bioprosthetic* aortic annulus size (see table below) Aortic Annulus Diameter Ascending Aorta Diameter 18 mm* - 20 mm>34 mm 20 mm - 23 mm >40 mm 23 mm - 27 mm >43 mm 27 mm - 29 mm >43 mm

    * 17mm for surgical bioprosthetic aortic annulus

  • Congenital bicuspid or unicuspid valve verified by echocardiography (Not applicable for TAV in SAV subjects).
  • Sinus of valsalva anatomy that would prevent adequate coronary perfusion.
  • Degenerated surgical bioprothesis presents with a significant concomitant perivalvular leak (between prothesis and native annulus), is not securely fixed in the native annulus, or is not structurally intact (e.g. wireform frame fracture) (ONLY FOR TAV in SAV subjects)
  • Degenerated surgical bioprothesis presents with a partially detached leaflet that in the aortic position may obstruct a coronary ostium (ONLY FOR TAV in SAV subjects)

Vascular

  • Transarterial access not able to accommodate an 18Fr sheath.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01675440

  Show 43 Study Locations
Sponsors and Collaborators
Medtronic Cardiovascular
  More Information

Responsible Party: Medtronic Cardiovascular
ClinicalTrials.gov Identifier: NCT01675440     History of Changes
Other Study ID Numbers: 10050361DOC 
Study First Received: August 22, 2012
Last Updated: April 26, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Constriction, Pathologic
Aortic Valve Stenosis
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction

ClinicalTrials.gov processed this record on August 25, 2016