Clinical trial NCT02672553: EDWARDS INTUITY Valve System CADENCE-MIS Study
Official title: A Randomized Comparison of the EDWARDS INTUITY Valve System anD commErcially Available Aortic Bioprostheses in Subjects uNdergoing surgiCal Aortic Valve Replacement Using Minimally InvaSive Techniques
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Valve Disease
Aortic Stenosis
Keywords: Aortic Valve Replacement
Minimal Invasive Sternotomy
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2016-02-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study purpose is to compare the EDWARDS INTUITY valve system in a minimal invasive surgical approach (MIS) with any commercially available aortic bioprosthesis in standard full sternotomy surgical approach.

Detailed description: This is a randomized study to compare the cross-clamp time (XCT) and cardiopulmonary bypass time (CPBT) of the EDWARDS INTUITY valve system in a minimally invasive surgical approach (MIS) with any commercially available aortic bioprosthesis in standard full sternotomy surgical approach, in patients with logistic EuroScore \< 20 undergoing elective isolated aortic valve replacement (AVR) surgery.

Additionally, the aim is to gather sufficient data to quantify the effect size of short term patient benefit outcomes previously identified from literature and to explore additional healthcare resource utilization endpoints.

Eligibility criteria: Inclusion:

1. adult male or female ≥18 years of age
2. symptomatic for aortic stenosis / mixed aortic stenosis and aortic insufficiency disease for which isolated surgical aortic valve replacement without concomitant procedures is planned
3. EuroSCORE \<20
4. NYHA Class ≥II
5. Subject has signed and dated the investigation informed consent form prior to study specific procedures are performed
6. Subject is geographically stable and agrees to participate in follow-up assessments as specified in the protocol and informed consent

Exclusion (i.a.):

1. pure aortic insufficiency
2. previous cardiac surgery (involved FS or MIS approach)
3. congenital true bicuspid / unicuspid aortic valve
4. requires emergency surgery or has had emergency surgery for any reason

   ≤ 1 month before the intended treatment
5. LVEF \<25%
6. active endocarditis ≤ 6 months before the intended treatment
7. acute MI ≤ 90 days before the intended treatment
8. had a stroke or transient ischemic attack within six months prior to scheduled aortic valve replacement surgery
9. oxygen or ventilator dependent
10. life expectancy \< 12 months
11. substance abuser
12. Female subject is pregnant or lactating
13. documented leukopenia (WBC \< 3.5x 103/μL), acute anemia (Hgb \< 10.0 gm/dL or \< 6.2 mmol/L), thrombocytopenia (platelet count \< 100x 103/mL), or history of bleeding diathesis or coagulopathy
14. hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or mechanical ventilation within 30 days of procedure
15. documented echocardiographic evidence of intracardiac mass, thrombus or vegetation
16. renal insufficiency as determined by Serum creatinine ≥ 200 μmol/L (2.27 mg/dL) at screening or end-stage renal disease requiring chronic dialysis
17. documented hyperparathyroidism
18. currently participating in an investigational drug or device trial for which follow-up has not yet been completed
19. Minimally Invasive access to the heart is not possible due to anatomical constraints or any other pre-existing condition

Intra-operative Exclusion:

1. has calcium on the anterior mitral leaflet which cannot be removed
2. has extensive calcification of the aortic root
3. Annular deformation which may or may not be caused by too extensive decalcification of the aortic annulus
4. has left atrial thrombus
5. The position of the coronary ostia relative to the EDWARDS INTUITY Valve would result in obstruction of blood flow
6. hemodynamically unstable during the procedure requiring the procedure to be aborted prior to insertion of the study bioprosthesis and delivery system
7. Study device is not available in the correct size for the subject

Primary outcomes:
measure: Median Subject Time Spent on Cardiopulmonary Cross Clamp
timeFrame: At time of surgery; an average of 1 hour
measure: Median Amount of Time Subject Spent on Cardiopulmonary Bypass
timeFrame: At time of surgery; an average of 1 hour
Secondary outcomes:
measure: Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at 2 Years.
timeFrame: Baseline and 2 Years.
measure: Subject's Average Mean Gradients (mmHg) Measurements Over Time.
timeFrame: Baseline, Discharge, 30 days, 3 Months, 1 Year
measure: Subject's Average Peak Gradients (mmHg) Measurements Over Time.
timeFrame: Baseline, Discharge, 30 days, 3 Months, 1 Year
measure: Subject's Effective Orifice Area (EOA) Measurement Over Time.
timeFrame: Baseline, Discharge, 30 days, 3 Months, 1 Year
measure: Amount of Paravalvular Leak Over Time.
timeFrame: Discharge, 30 days, 3 month, 1 year
measure: Conversion of Edwards INTUITY Surgical Aortic Valve to Control Surgical Aortic Heart Valves During Surgery.
timeFrame: Prior to Surgery
measure: Subjects Who Required a Thoracic Resternotomy Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects Who Received a Permanent Pacemaker Over Time.
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Paravalvular Leak > or Equal to 3+ and/or Requiring Intervention Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects Who Experienced Major Bleeding Over Time.
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects Who Experienced Respiratory Failure Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Cerebral Vascular Accident or Permanent Stroke Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With Renal Failure Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With Endocarditis Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Deep Sternal Would Infection Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Myocardial Infarction Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Thromboembolism Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Cardiac Tamponade Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Subjects With a Cardiac Reoperation for Any Reason Over Time
timeFrame: 30 days, 3 Months, 1 Year, 2 Years.
measure: Conversion of Subjects Undergoing Minimally Invasive Surgical Incision to Full Sternotomy for the Randomized to Edwards INTUITY Group During Surgery.
timeFrame: Prior to Surgery
measure: Subject's Average Score on the EQ-5D - Quality of Life Questionnaire Over Time
timeFrame: Baseline, 30 days, 3 Months, 1 Year
measure: Subject's Average Score SF-12 - Quality of Life Questionnaire Over Time
timeFrame: Baseline, 30 days, 3 Months, 1 Year
measure: Subject's Average Score on the KCCQ - Quality of Life Questionnaire Over Time
timeFrame: Baseline, 30 days, 3 Months, 1 Year
measure: Health Care Utilization
timeFrame: Day of surgical procedure through discharge from the hospital, an average of 1.5 weeks
measure: Subject's Effective Orifice Area Index (EOAI) Measurement Over Time.
timeFrame: Baseline, Discharge, 30 days, 3 Months, 1 Year
measure: Amount of Aortic Valvular Regurgitation Over Time.
timeFrame: Discharge, 30 days, 3 month, 1 year
Other outcomes:
Locations:
city: Leipzig
country: Germany
facility: Leipzig Heart Center
state: Saxony
Study officials:
affiliation: Leipzig Heart Center
name: Prof. Borger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Borger MA, Dohmen PM, Knosalla C, Hammerschmidt R, Merk DR, Richter M, Doenst T, Conradi L, Treede H, Moustafine V, Holzhey DM, Duhay F, Strauch J. Haemodynamic benefits of rapid deployment aortic valve replacement via a minimally invasive approach: 1-year results of a prospective multicentre randomized controlled trial. Eur J Cardiothorac Surg. 2016 Oct;50(4):713-720. doi: 10.1093/ejcts/ezw042. Epub 2016 Mar 2.
citation: Borger MA, Moustafine V, Conradi L, Knosalla C, Richter M, Merk DR, Doenst T, Hammerschmidt R, Treede H, Dohmen P, Strauch JT. A randomized multicenter trial of minimally invasive rapid deployment versus conventional full sternotomy aortic valve replacement. Ann Thorac Surg. 2015 Jan;99(1):17-25. doi: 10.1016/j.athoracsur.2014.09.022. Epub 2014 Nov 20.