EDWARDS INTUITY Valve System CADENCE-MIS Study (CADENCE-MIS)

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

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.

Study Overview

• Status: Completed
• Conditions: Aortic Stenosis; Aortic Valve Disease
• Intervention / Treatment: Device: EDWARDS INTUITY Valve System, Model 8300A; Device: Stented Aortic Bioprostheses

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Saxony
    • Leipzig, Saxony, Germany, 04289
      • Leipzig Heart Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EDWARDS INTUITY; EDWARDS INTUITY Valve System, Model 8300A	Device: EDWARDS INTUITY Valve System, Model 8300A; To evaluate cardiac performance characteristics and adverse events rates associated with the EDWARDS INTUITY Valve in patients undergoing MIS-AVR.; Other Names: aortic stenosis; stenosis-based insufficiency; aortic valve replacement
Active Comparator: Stented Aortic Bioprostheses	Device: Stented Aortic Bioprostheses; In comparison to control valves available on the market undergoing FS-AVR; Other Names: aortic stenosis; stenosis-based insufficiency; aortic valve replacement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Subject Time Spent on Cardiopulmonary Cross Clamp	Cardiopulmonary cross clamp time is the amount of time that the patient's aorta (blood vessel) is clamped by a surgical instrument used in cardiac surgery. This allows the normal blood flow to be sent to an artificial heart and lung machine to keep it at a constant temperature and oxygen level.	At time of surgery; an average of 1 hour
Median Amount of Time Subject Spent on Cardiopulmonary Bypass	Cardiopulmonary bypass time is the amount of time that the patient's blood circulates through an artificial heart and lung machine during cardiac surgery.	At time of surgery; an average of 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at 2 Years.	The New York Heart Association (NYHA) functional classification system relates symptoms to everyday activities and the patient's quality of life. Class I. Patients with cardiac disease but without resulting limitation of physical activity. Class II. Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Class III. Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Class IV. Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest.	Baseline and 2 Years.
Subject's Average Mean Gradients (mmHg) Measurements Over Time.	Mean gradient is the average flow of blood through the aortic valve measured in millimeters of mercury. Gradients are evaluated by echocardiography over time. Mean gradient values depend on the size and type of valve.	Baseline, Discharge, 30 days, 3 Months, 1 Year
Subject's Average Peak Gradients (mmHg) Measurements Over Time.	Peak gradient is the maximum value measured of flow of blood through the aortic valve as measured in millimeters of mercury. Gradients are evaluated by echocardiography over time.	Baseline, Discharge, 30 days, 3 Months, 1 Year
Subject's Effective Orifice Area (EOA) Measurement Over Time.	Effective orifice area represents the cross-sectional area of the blood flow downstream of the aortic valve. Effective orifice area is evaluated by echocardiography over time.	Baseline, Discharge, 30 days, 3 Months, 1 Year
Amount of Paravalvular Leak Over Time.	Number of subjects who experienced a Paravalvular Leak shown over various time points. Paravalvular leak refers to blood flowing through a channel between the implanted artificial valve and the cardiac tissue as a result of inappropriate sealing. Paravalvular leak is evaluated by echocardiography over time. It is assessed on a scale from minimum of 0 to maximum of 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. Higher numbers on the scale show a worsening outcome.	Discharge, 30 days, 3 month, 1 year
Conversion of Edwards INTUITY Surgical Aortic Valve to Control Surgical Aortic Heart Valves During Surgery.	Subjects randomized to the Edwards INTUITY group that were converted to the control group and received commercially available surgical aortic heart valves during surgery.	Prior to Surgery
Subjects Who Required a Thoracic Resternotomy Over Time	Number of Subjects who had a surgical opening of their chest after their initial aortic heart valve surgery shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Subjects Who Received a Permanent Pacemaker Over Time.	Number of Subjects who received a Permanent Pacemaker shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Paravalvular Leak > or Equal to 3+ and/or Requiring Intervention Over Time	Number of subjects who experienced a Paravalvular Leak shown over various time points. Paravalvular leak refers to blood flowing through a channel between the implanted artificial valve and the cardiac tissue as a result of inappropriate sealing. Paravalvular leak is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 = no leak, 1 = a trace leak, 2 = a mild leak, 3 = a moderate leak, and 4 = a severe leak. Higher numbers on the scale show a worsening outcome.	30 days, 3 Months, 1 Year, 2 Years.
Subjects Who Experienced Major Bleeding Over Time.	Number of subjects who experienced Major Bleeding shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Subjects Who Experienced Respiratory Failure Over Time	Number of subjects who experienced a Respiratory Failure shown over various time points. Respiratory failure happens when not enough oxygen passes from your lungs to your blood.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Cerebral Vascular Accident or Permanent Stroke Over Time	Number of subjects who experienced a Cerebral Vascular Accident or Permanent Stroke shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With Renal Failure Over Time	Number of subjects who experienced Renal (kidney) Failure shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With Endocarditis Over Time	Number of subjects who experienced Endocarditis shown over various time points. Endocarditis is an infection of the endocardium, which is the inner lining of your heart chambers and heart valves.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Deep Sternal Would Infection Over Time	Number of subjects who experienced a Deep Sternal Wound Infection shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Myocardial Infarction Over Time	Number of subjects who experienced a Myocardial Infarction shown over various time points. A Myocardial infarction, commonly known as a heart attack, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Thromboembolism Over Time	Number of subjects who experienced a Thromboembolism shown over various time points. A thromboembolism is an obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Cardiac Tamponade Over Time	Number of subjects who experienced a Cardiac Tamponade shown over various time points. Cardiac tamponade is when fluid in the pericardium (the sac around the heart) builds up and results in compression (squeezing) of the heart.	30 days, 3 Months, 1 Year, 2 Years.
Subjects With a Cardiac Reoperation for Any Reason Over Time	Number of subjects who experienced a Cardiac reoperation for any reason shown over various time points.	30 days, 3 Months, 1 Year, 2 Years.
Conversion of Subjects Undergoing Minimally Invasive Surgical Incision to Full Sternotomy for the Randomized to Edwards INTUITY Group During Surgery.	Subjects Randomized to Edwards INTUITY Group's Surgical Aortic Valve undergoing Minimally Invasive Surgical incision being converted to a Full Sternotomy open procedure During Surgery.	Prior to Surgery
Subject's Average Score on the EQ-5D - Quality of Life Questionnaire Over Time	The EuroQol-5 Dimension (EQ-5D) is a standardized questionnaire that asks subjects to rate themselves (no problems, some problems, extreme problems) on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scale is indexed and ranges from a minimum of 0.275 and a maximum of 1.000. A lower number indicates the participants experiences more problems and a higher number indicates the participants experiences fewer problems.	Baseline, 30 days, 3 Months, 1 Year
Subject's Average Score SF-12 - Quality of Life Questionnaire Over Time	Subject's Average Score at Baseline and at each follow-up interval until 2 year - SF-12. The Medical Outcomes Study Short-Form 12 (SF-12) - Physical Component Summary (PCS) and Mental Component Summary (MCS). The SF-12 questionnaire scale ranges from 100, which reflects the best health status to 0, which reflects the worse health status.	Baseline, 30 days, 3 Months, 1 Year
Subject's Average Score on the KCCQ - Quality of Life Questionnaire Over Time	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores range from 0-100, in which higher scores reflect better health status. Subjects took this questionnaire at Baseline, 30 days, 3 Months,and 1 Year.	Baseline, 30 days, 3 Months, 1 Year
Health Care Utilization	The average amount of time the subjects spent in the intensive care unit, the intermediate care length of stay, and the average total length of hospital stay after their heart valve replacement procedure.	Day of surgical procedure through discharge from the hospital, an average of 1.5 weeks
Subject's Effective Orifice Area Index (EOAI) Measurement Over Time.	Effective orifice area index represents the minimal cross-sectional area of the blood flow downstream of the aortic valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time.	Baseline, Discharge, 30 days, 3 Months, 1 Year
Amount of Aortic Valvular Regurgitation Over Time.	Aortic valvular regurgitation occurs when the aortic valve in the heart does not close tightly allowing some of the blood that was pumped out of the heart to leak back into it. Aortic valvular regurgitation is evaluated by echocardiography over time. It is assessed on a scale from 0 to 4, where 0 represents no regurgitation and 4 represents severe regurgitation. Higher numbers on the scale show a worsening outcome.	Discharge, 30 days, 3 month, 1 year

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Prof. Borger, MD, Leipzig Heart Center

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Short Form Health Survey (SF-12) with 12 questions to measure functional health and well-being of patient's quality of life
• EuroQol Standardized Instrument (EQ-5D) developed to measure of health-related quality of life.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: November 6, 2015
• First Submitted That Met QC Criteria: January 29, 2016
• First Posted (Estimate): February 3, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Aortic Valve Replacement; Minimal Invasive Sternotomy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Aortic Valve Disease
• Other Study ID Numbers: 2011-12 (Other Identifier: AP HM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: As of this date no IPD plan has been formulated.