Clinical trial NCT01634269: Clinical Evaluation of MDT-2111 in Subjects With Small Aortic Annuli and Symptomatic Severe Aortic Stenosis
Official title: Medtronic MDT-2111 CoreValve Japan 23mm Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: Valvular Heart Disease
Severe Aortic Stenosis
Aortic Valve Replacement
Lead sponsor: Medtronic Cardiovascular
Sponsor class: INDUSTRY
First posted: 2012-07-06
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the present trial is to demonstrate the safety and effectiveness of the MDT-2111 in the treatment of symptomatic severe aortic stenosis in subjects with small aortic annuli and deemed difficult for surgical operation.

Detailed description: The purpose of this trial is to evaluate the effectiveness and safety of the MDT-2111 TAV system in subjects with small annuli and symptomatic severe AS deemed difficult for surgical intervention. The primary endpoint is a composite of functional effectiveness as measured by improvement of at least 1 New York Heart Association (NYHA) class from baseline to 6 months and anatomical effectiveness as measured by Effective Orifice Area (EOA) ≥1.0 cm² at 6 months.

Eligibility criteria: Inclusion Criteria:

1. Subject must have co-morbidities such that one cardiologist and one cardiac surgeon agree that medical factors preclude operation, based on a conclusion that the probability of death or serious morbidity exceeds the probability of meaningful improvement.
2. Subject has senile degenerative aortic valve stenosis with:

   mean gradient \> 40 mmHg or jet velocity greater than 4.0 m/s 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.
3. Subject is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA Functional Class Class III or greater. If screening committee agrees the eligibility of a patient with class II , based on medical factors, he/she can be enrolled.
4. Patient has been informed of the nature of the trial and has signed an Informed Consent Form.
5. Patient agrees to comply with specified follow-up evaluations and to return to the same investigational site where the procedure was performed.

Exclusion Criteria:

1. Evidence of an acute myocardial infarction ≤ 30 days prior to the intended treatment.
2. Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the procedure.
3. Blood dyscrasias as defined:

   * Leukopenia (WBC count \< 1,000 cells/mm³)
   * Thrombocytopenia (platelet count \<50,000 cells/mm³)
   * History of bleeding diathesis or coagulopathy
   * Hypercoagulable states
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.
10. GI bleeding within the past 3 months.
11. A known hypersensitivity or contraindication to any of the following which cannot be adequately pre-medicated:

    * Aspirin
    * Ticlopidine
    * Heparin
    * Contrast media
    * Nitinol (titanium and nickel alloy)
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. Note: Trials requiring extended follow-up for products that were investigational, but have since become commercially available, are not considered investigational trials.
18. Symptomatic carotid or vertebral artery disease.
19. Native aortic annulus size \< 18 mm or \> 20 mm per the screening diagnostic imaging.
20. Pre-existing prosthetic heart valve in any position.
21. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation).
22. Mitral regurgitation (moderate to severe) or severe tricuspid regurgitation.
23. Moderate to severe mitral stenosis.
24. Hypertrophic obstructive cardiomyopathy.
25. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
26. Severe basal septal hypertrophy with an outflow gradient.
27. Ascending aorta diameter \> 34 mm
28. Congenital bicuspid or unicuspid valve verified by echocardiography.
29. For patients with native coronary artery dependent circulation:

    * Sinus of valsalva width \< 25 mm OR
    * Height of the left or right coronary sinus of valsalva (to the tubular aorta) \< 15mm.
30. Femoral or iliac artery of the first choice corresponding to any one of the following:

    * Angle at aortic root (the angle between aortic valve annulus plane and horizontal plane/vertebra) exceeds 70°.
    * Vessel diameter of femoral or iliac artery is less than 6 mm.
    * Aorta has severe calcification, excess tortuosity or severe atherosclerosis.
    * Transarterial access not able to accommodate an 18Fr sheath.
31. Subclavian artery of the second choice corresponding to any one of the following:

    * Angle at aortic root (the angle between aortic valve annulus plane and horizontal plane/vertebra) exceeds 70° (in the case of left subclavian artery) and 30° (in the case of right subclavian artery).
    * Vessel diameter of subclavian artery is less than 6 mm.
    * Transarterial access not able to accommodate an 18Fr sheath.
32. Direct Aortic Artery as third line choice of access. Patients are excluded from Direct Aortic access if:

    * Access site is less than 6 cm from the aortic valve basal plane
    * Access site has calcification or porcelain aorta
    * Access site and delivery trajectory contain RIMA or patent RIMA graft

Primary outcomes:
measure: Composite Score of Change in New York Heart Association (NYHA) Class and Effective Orifice Area (EOA).
timeFrame: baseline and 6 months
Secondary outcomes:
measure: New York Heart Classification (NYHA) Over Time
timeFrame: 30 days
measure: New York Heart Classification (NYHA) Over Time
timeFrame: 6 months
measure: New York Heart Classification (NYHA) Over Time
timeFrame: 12 months
measure: New York Heart Classification (NYHA) Over Time
timeFrame: 24 months
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
timeFrame: 0 day to 30 days
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
timeFrame: 0 day to 6 months
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
timeFrame: 0 day to 12 months
measure: Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)
timeFrame: 0 day to 24 months
measure: Device Success as Defined in the Description.
timeFrame: after procedure or discharge
measure: Procedural Success, Defined as Device Success and Absence of In-hospital MACCE
timeFrame: from admission for procedure to discharge
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient
timeFrame: 30 days
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient
timeFrame: 6 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient
timeFrame: 12 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient
timeFrame: 24 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Effective Orifice Area (EOA)
timeFrame: 30 days
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Effective Orifice Area (EOA)
timeFrame: 6 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Effective Orifice Area (EOA)
timeFrame: 12 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Effective Orifice Area (EOA)
timeFrame: 24 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)
timeFrame: 30 days
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)
timeFrame: 6 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)
timeFrame: 12 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)
timeFrame: 24 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Regurgitation (Transvalvular & Paravalvular) (Total AR)
timeFrame: 30 days
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Regurgitation (Transvalvular & Paravalvular) (Total AR)
timeFrame: 6 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Regurgitation (Transvalvular & Paravalvular) (Total AR)
timeFrame: 12 months
measure: Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Regurgitation (Transvalvular & Paravalvular) (Total AR)
timeFrame: 24 months
measure: Repeat Hospitalization
timeFrame: 0 day to 30 days
measure: Repeat Hospitalization
timeFrame: 0 day to 6 months
measure: Repeat Hospitalization
timeFrame: 0 day to 12 months
measure: Repeat Hospitalization
timeFrame: 0 day to 24 months
measure: Valve-related Deaths
timeFrame: 0 day to 30 days
measure: Valve-related Deaths
timeFrame: 0 day to 6 months
measure: Valve-related Deaths
timeFrame: 0 day to 12 months
measure: Valve-related Deaths
timeFrame: 0 day to 24 months
measure: Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline)
timeFrame: Baseline to 30 days
measure: Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline)
timeFrame: Baseline to 6 months
measure: Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline)
timeFrame: Baseline to 12 months
measure: Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline)
timeFrame: Baseline to 24 months
Other outcomes:
Locations:
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital
state: Kanagawa
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Hidaka
country: Japan
facility: Saitama Medical University
state: Saitama
Study officials:
affiliation: Osaka University Hospital
name: Yoshi Sawa, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sawa Y, Torikai K, Kobayashi J, Niinami H, Kuratani T, Maeda K, Kanzaki H, Komiyama N, Tanaka Y, Zhang A, Saito S. Midterm Outcomes With a Self-Expandable Transcatheter Heart Valve in Japanese Patients With Symptomatic Severe Aortic Stenosis. Circ J. 2017 Jul 25;81(8):1108-1115. doi: 10.1253/circj.CJ-17-0112. Epub 2017 Mar 17.