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Completed

NCT Number: NCT01437098

Clinical Evaluation of MDT-2111 in Subjects With Symptomatic Severe Aortic Stenosis

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

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Key information

Conditions

Aortic Valve Stenosis Aortic Valve Disease Cardiovascular Diseases Heart Diseases Heart Valve Diseases Ventricular Outflow Obstruction

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan

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About this study

Non-randomized, prospective, multicenter, single-arm trial.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subject must have co-morbidities such that one cardiologist and one 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.
  • 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.

  • 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.
  • Subject has been informed of the nature of the trial and has signed an Informed Consent Form.
  • Subject agrees to comply with specified follow-up evaluations and to return to the same investigational site where the procedure was performed.

Exclusion criteria

  • Evidence of an acute myocardial infarction ≤ 30 days prior to the intended treatment.
  • Any percutaneous coronary or peripheral interventional procedure performed within 30 days prior to the procedure.
  • 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
  • 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).
  • End stage renal disease requiring chronic dialysis.
  • GI bleeding within the past 3 months.
  • 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)
  • 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 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).
  • 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.
  • Symptomatic carotid or vertebral artery disease.
  • Native aortic annulus size < 20 mm or > 27 mm per the screening diagnostic imaging.
  • Pre-existing prosthetic heart valve in any position.
  • Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant aortic regurgitation).
  • Mitral regurgitation (moderate to severe) or severe tricuspid regurgitation.
  • Moderate to severe mitral stenosis.
  • Hypertrophic obstructive cardiomyopathy.
  • Echocardiographic evidence of intracardiac mass, thrombus or vegetation.
  • Severe basal septal hypertrophy with an outflow gradient.
  • Ascending aorta diameter > 43 mm (in case of the aortic annulus is 23-27 mm) unless the aortic annulus is 20-23 mm in which case the ascending aorta diameter > 40 mm.
  • Congenital bicuspid or unicuspid valve verified by echocardiography.
  • For patients with native coronary artery dependent circulation:
  • Sinus of valsalva width < 29 mm unless the aortic annulus is 20-23 mm, in which case the sinus of valsalva width < 27 mm, OR
  • Height of the left or right coronary sinus of valsalva (to the tubular aorta) < 15mm.
  • Femoral or iliac artery of the first choice corresponding to any one of the followings:
  • 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.
  • Subclavian artery of the second choice corresponding to any one of the followings:
  • 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.
  • 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

Treatment and study plan

MDT-2111 CoreValve for TAVI

Device

CoreValve Transcatheter Aortic Valve Implantation (TAVI) using the MDT-2111 system.

Primary outcomes

  1. Composite Success of Improvement in New York Heart Association (NYHA) Class and a Performance Goal for Effective Orifice Area (EOA).

    Time frame: baseline and 6 months

    The primary endpoint was defined as the proportion of implanted subjects with improvement of at least 1 NYHA class from baseline to 6 months and EOA greater than 1.2 cm² at 6 months.

Secondary outcomes

  1. NYHA Classification Over Time

    Time frame: 30 days

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA) Class I Subject with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

    Class II Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

  2. NYHA Classification Over Time

    Time frame: 6 months

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA) Class I Subject with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

    Class II Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

  3. NYHA Classification Over Time

    Time frame: 12 Months

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA) Class I Subject with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

    Class II Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.

    Class IV Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

  4. NYHA Classification Over Time

    Time frame: 24 Months

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA) Class I Subject with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

    Class II Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.

    Class IV Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

  5. NYHA Classification Over Time

    Time frame: 36 Months

    NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA) Class I Subject with cardiac disease but without resulting limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.

    Class II Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain.

    Class III Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain.

    Class IV Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.

  6. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)

    Time frame: 0 day to 30 days

    MACCE is defined as a composite of:

    • all-cause death
    • myocardial infarction (MI)
    • all stroke, and
    • reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

  7. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)

    Time frame: 0 day to 6 months

    MACCE is defined as a composite of:

    • all-cause death
    • myocardial infarction (MI)
    • all stroke, and
    • reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

  8. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)

    Time frame: 0 day to 12 months

    MACCE is defined as a composite of:

    • all-cause death
    • myocardial infarction (MI)
    • all stroke, and
    • reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

  9. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)

    Time frame: 0 day to 24 months

    MACCE is defined as a composite of:

    • all-cause death
    • myocardial infarction (MI)
    • all stroke, and
    • reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

  10. Major Adverse Cardiovascular and Cerebrovascular Event (MACCE)

    Time frame: 0 day to 36 months

    MACCE is defined as a composite of:

    • all-cause death
    • myocardial infarction (MI)
    • all stroke, and
    • reintervention (defined as any cardiac surgery or percutaneous reintervention catheter procedure that repairs, otherwise alters or adjusts, or replaces a previously implanted valve)

  11. Device Success as Defined in the Description.

    Time frame: after procedure or discharge

    • 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 (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 AR)
    • Only one valve implanted in the proper anatomical location

  12. Procedural Success, Defined as Device Success and Absence of In-hospital MACCE.

    Time frame: after procedure or discharge

  13. Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient

    Time frame: 30 days

  14. Echocardiographic Assessment of Prosthetic Valve Performance- Mean Gradient

    Time frame: 6 months

  15. Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient

    Time frame: 12 months

  16. Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient

    Time frame: 24 months

  17. Echocardiographic Assessment of Prosthetic Valve Performance - Mean Gradient

    Time frame: 36 months

  18. Echocardiographic Assessment of Prosthetic Valve Performance- Effective Orifice Area (EOA)

    Time frame: 30 days

  19. Echocardiographic Assessment of Prosthetic Valve Performance- Effective Orifice Area (EOA)

    Time frame: 6 months

  20. Echocardiographic Assessment of Prosthetic Valve Performance- Effective Orifice Area (EOA)

    Time frame: 12 months

  21. Echocardiographic Assessment of Prosthetic Valve Performance- Effective Orifice Area (EOA)

    Time frame: 24 months

  22. Echocardiographic Assessment of Prosthetic Valve Performance- Effective Orifice Area (EOA)

    Time frame: 36 months

  23. Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)

    Time frame: 30 days

  24. Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)

    Time frame: 6 months

  25. Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)

    Time frame: 12 months

  26. Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)

    Time frame: 24 months

  27. Echocardiographic Assessment of Prosthetic Valve Performance - Left Ventricular Ejection Fraction (LVEF)

    Time frame: 36 months

  28. Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Valve Regurgitation (Transvalvular & Paravalvular) (Total AR)

    Time frame: 30 days

  29. Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Valve Regurgitation (Transvalvular & Paravalvular) (Total AR)

    Time frame: 6 months

  30. Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Valve Regurgitation (Transvalvular & Paravalvular) (Total AR)

    Time frame: 12 months

  31. Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Valve Regurgitation (Transvalvular & Paravalvular) (Total AR)

    Time frame: 24 months

  32. Echocardiographic Assessment of Prosthetic Valve Performance - Total Aortic Valve Regurgitation (Transvalvular & Paravalvular) (Total AR)

    Time frame: 36 months

  33. Repeat Hospitalization

    Time frame: 0 day to 30 days

  34. Repeat Hospitalization

    Time frame: 0 day to 6 months

  35. Repeat Hospitalization

    Time frame: 0 day to 12 months

  36. Repeat Hospitalization

    Time frame: 0 day to 24 months

  37. Repeat Hospitalization

    Time frame: 0 day to 36 months

  38. Valve-related Deaths

    Time frame: 0 day to 30 days

  39. Valve-related Deaths

    Time frame: 0 day to 6 months

  40. Valve-Related Deaths

    Time frame: 0 day to 12 months

  41. Valve-related Deaths

    Time frame: 0 day to 24 months

  42. Valve-related Deaths

    Time frame: 0 day to 36 months

  43. Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline) (Q of L)

    Time frame: Baseline to 30 days

    The SF-36 assessment was used to evaluate subject Quality of life (QoL) by assessing change in physical function and general health status. The SF-36 v2TM Scoring Program2,3 was used to convert raw scores ranging from 0 to 100 into norm-based scores, allowing direct comparison to the reference values for the Japanese population. A norm-based score of less than 50 was interpreted as below average when compared to the Japanese population whereas norm-based scores greater than 50 were interpreted as above average.

  44. Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline) (Q of L)

    Time frame: Baseline to 6 months

    The SF-36 assessment was used to evaluate subject Quality of life (QoL) by assessing change in physical function and general health status. The SF-36 v2TM Scoring Program2,3 was used to convert raw scores ranging from 0 to 100 into norm-based scores, allowing direct comparison to the reference values for the Japanese population. A norm-based score of less than 50 was interpreted as below average when compared to the Japanese population whereas norm-based scores greater than 50 were interpreted as above average.

  45. Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline) (Q of L)

    Time frame: Baseline to 12 months

    The SF-36 assessment was used to evaluate subject Quality of life (QoL) by assessing change in physical function and general health status. The SF-36 v2TM Scoring Program2,3 was used to convert raw scores ranging from 0 to 100 into norm-based scores, allowing direct comparison to the reference values for the Japanese population. A norm-based score of less than 50 was interpreted as below average when compared to the Japanese population whereas norm-based scores greater than 50 were interpreted as above average.

  46. Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline) (Q of L)

    Time frame: Baseline to 24 Months

    The SF-36 assessment was used to evaluate subject Quality of life (QoL) by assessing change in physical function and general health status. The SF-36 v2TM Scoring Program2,3 was used to convert raw scores ranging from 0 to 100 into norm-based scores, allowing direct comparison to the reference values for the Japanese population. A norm-based score of less than 50 was interpreted as below average when compared to the Japanese population whereas norm-based scores greater than 50 were interpreted as above average.

  47. Quality of Life Assessment Using SF-36 Questionnaire - Physical Component Summary (Paired Change From Baseline) (Q of L)

    Time frame: Baseline to 36 Months

    The SF-36 assessment was used to evaluate subject Quality of life (QoL) by assessing change in physical function and general health status. The SF-36 v2TM Scoring Program2,3 was used to convert raw scores ranging from 0 to 100 into norm-based scores, allowing direct comparison to the reference values for the Japanese population. A norm-based score of less than 50 was interpreted as below average when compared to the Japanese population whereas norm-based scores greater than 50 were interpreted as above average.

Sponsors and collaborators

Lead sponsor

Medtronic Cardiovascular

Industry

Registry information

Important dates

Study start
2011
Primary completion
2013
Study completion
2018
First posted
Sep 20, 2011
Registry last updated
Feb 15, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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