Surgical Treatment of Aortic Stenosis With a Next Generation, Rapid Deployment Surgical Aortic Valve (TRANSFORM™)

Multi-CenTer Experience With the Rapid Deployment EDWARDS INTUITY Valve System FOR Aortic Valve ReplaceMent

The purpose of the clinical study is to prove that the heart valve device is safe, effective, and performs as intended.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis; Aortic Valve Stenosis With Insufficiency; Regurgitation, Aortic Valve; Aortic Valve Incompetence
• Intervention / Treatment: Device: EDWARDS INTUITY valve

Detailed Description

This is a prospective, non-randomized, multi-center trial. Up to 950 subjects will be enrolled at up to 35 centers in the US. After replacement of their aortic heart valve with the EDWARDS INTUITY valve system, each patient will have routine follow-up tests at the following intervals: discharge, 3 months, 1 year, and annually thereafter for a minimum of five years.

• Study Type: Interventional
• Enrollment (Actual): 934
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90033
      • Keck Hospital of University of Southern California
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
  • Florida
    • Orlando, Florida, United States, 32803
      • Florida Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The University of Michigan Medical School
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University - Barnes Jewish Hospital
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore Long Island Jewish Health System
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17010
      • Pinnacle Health at Harrisburg Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Memorial Hospital
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Health
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St Luke's Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Inclusion Criteria - Subjects will be required to meet all inclusion criteria:

  1. Male or female, age 18 years or older
  2. Has aortic stenosis or stenosis-insufficiency of an aortic valve requiring a planned replacement as indicated in the preoperative evaluation
  3. Is scheduled to undergo planned aortic valve replacement with or without concomitant coronary bypass surgery
  4. Provide written informed consent
  5. Geographically stable and agrees to attend follow-up assessments until all subjects have completed 5 years of follow up

Exclusion Criteria:

- Exclusion Criteria - Subjects will not be eligible for trial participation if any of the following criteria are present:

1. Pure aortic insufficiency
2. Requires emergency surgery
3. Previous aortic valve replacement
4. Had prior mitral, tricuspid or pulmonic valve surgery, which included implant of a bioprosthetic valve, mechanical valve, or annuloplasty ring that will remain in situ
5. Requires multiple valve replacement/repair
6. Requires a surgical procedure outside of the cardiac area (e.g., vascular endarterectomy, vascular bypass, tumor removal)
7. Aneurysm of the aortic root and/or ascending aorta requiring surgical intervention
8. Active endocarditis/myocarditis or endocarditis/ myocarditis within 3 months prior to the scheduled AVR surgery
9. Myocardial infarction (MI) within thirty (30) days prior to valve replacement surgery
10. Renal insufficiency as determined by creatinine ≥ 2.5 mg/dL at screening or end-stage renal disease requiring chronic dialysis
11. Hyperparathyroidism
12. MRI or CT-scan confirmed cerebrovascular accident (CVA), or transient ischemic attack (TIA) within 6 months (180 days) of the procedure
13. Presence of non-cardiac disease limiting life expectancy to less than 12 months
14. Hypertrophic obstructive cardiomyopathy (HOCM)
15. Left ventricular ejection fraction ≤ 25%
16. Documented history of substance (drug or alcohol) abuse within the last 5 years
17. Echocardiographic evidence of an intra-cardiac mass, thrombus, or vegetation
18. Hemodynamic or respiratory instability requiring inotropic support, mechanical circulatory support, or mechanical ventilation within 30 days prior to the procedure
19. Pregnancy, lactation, or planning to become pregnant;
20. Currently incarcerated or unable to give voluntary informed consent
21. Leucopenia (WBC < 3.5x 103/µL), or acute anemia (Hgb < 10.0 gm/dL or 6 mmol/L), or thrombocytopenia (platelet count < 50x 103/µL), or history of bleeding diathesis or coagulopathy
22. History of myxomatous disease/connective tissue disorders (e.g., Marfan's Syndrome)

23. Current or recent participation (within 6 weeks prior to surgery) in an investigational drug or device trial

    • Intra-operative Exclusion Criteria

24. Anatomic variances which contraindicate implant of the trial valve, such as:

    1. anomalous coronary arteries
    2. annular deformation or extensive calcification of the annulus or aortic root which cannot be removed
    3. significant calcium on the anterior mitral leaflet
    4. pronounced septal calcification
    5. position of coronary ostia relative to Model 8300ACD valve that would result in obstruction of blood flow
25. Available devices are not suitably sized for the subject's annulus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDWARDS INTUITY valve; All subjects enrolled into the study are implanted with the EDWARDS INTUITY Valve System.	Device: EDWARDS INTUITY valve; Surgical replacement of the aortic valve with the EDWARDS INTUITY valve.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Late Adverse Events Divided by Late Patient Years (Expressed as a Percentage) for the INTUTY Valve Implanted Cohort	Late patient years are calculated from 31 days post-implant to the date of the last follow-up visits (or contact) or adverse events. Late Patient year calculation:[(Number of late adverse events/sum of late patient years) x 100]	Events occurring ≥ 31 days and up through 8 years post-implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Edwards INTUITY Surgical Aortic Heart Valve Device Technical Success	Device technical success is defined as the successful delivery and deployment of the aortic trial heart valve with maximum of two attempts and subject leaving the operating room (OR) with valve in place.	Day of procedure
Percentage of Subjects With Edwards INTUITY Surgical Heart Valve Procedural Success	Procedural success is defined as device technical success followed by the absence of adverse events resulting in device reoperation implant of permanent pacemaker (with baseline sinus rhythm and no other pre-existing conduction issues), or valve-related death within discharge or 10 days post index procedure, whichever comes first.	Day of procedure through discharge or 10 days post index procedure, whichever comes first.
Average Amount of Time Subject Spent on Cardiopulmonary Bypass	Surgical and hospitalization factors - Cardiopulmonary bypass time	Day of procedure
Average Subject Time on Cardiopulmonary Cross Clamp	Surgical and hospitalization factors - Cardiopulmonary cross clamp time	Day of procedure
Average Number of Days Subjects Were in the Intensive Care Unit (ICU)	Length of time surgical subjects were in the intensive care unit (ICU) after their heart valve replacement procedure.	Day of procedure through discharge from the hospital
Subject's New York Heart Association (NYHA) Classification Over Time	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, 3-months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8 Years
Subject's Average Mean Gradient 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. In general, a higher value is considered worse, and a lower value is considered better but the value is dependent on the size and type of valve.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8-Years follow-up
Subject's Average Peak Gradient 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. In general, a higher valve is considered worse, and a lower value is considered better, but the value is dependent on the size and type of valve.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8-Years follow-up
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. In general, a higher value is considered better, and a lower value is considered worse, but the value is dependent on the size and type of valve.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
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 mitral valve divided by the person's body surface area. Effective orifice area index is evaluated by echocardiography over time. In general, a higher value is considered better, and a lower value is considered worse, but the value is dependent on the size of the patient and the size and type of valve.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Performance Index Measurement Over Time	Performance index is defined as the subject's effective orifice area (the cross-sectional area of the blood flow downstream of the aortic valve) divided by the subject's native orifice area. Performance Index is evaluated by echocardiography over time and are dependent on the size and type of the valve. In general, a higher value is considered better, and a lower value is considered worse, but the value is dependent on the size of the patient and the size and type of valve.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Cardiac Output Measurement at Over Time	Cardiac output is the amount of blood the heart pumps through the circulatory system in a minute. Cardiac output is evaluated by echocardiography over time. Normal cardiac output in healthy volunteers over 60 years of age was reported between 3.1 and 6.4 liters per minute. In general, a higher value is considered better, and a lower value is considered worse.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Cardiac Index Measurement Over Time	Hemodynamic performance - Cardiac index (CI) evaluated by echocardiography. Cardiac index is an assessment of the cardiac output value based on the patient's size. To obtain the cardiac index, divide the cardiac output by the person's body surface area (BSA). Cardiac Index is a useful marker of how well the heart is functioning as a pump by directly correlating the volume of blood pumped by the heart with an individual's body surface area. Normal cardiac output index in healthy volunteers over 60 years of age was reported between 1.1 and 3.2 L/min/m^2. In general, a higher value is considered better, and a lower value is considered worse, but the value is dependent on the size of the patient.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Amount of Aortic Valvular Regurgitation in Subjects Over Time by Valve Size	Valvular regurgitation occurs when the 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. 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, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject's Average Score at Baseline and 1 Year on the Quality of Life Survey	The Medical Outcomes Study Short-Form 12 (SF-12) - physical and metal states. The SF-12 questionnaire scale ranges from 100, which reflects the best health status to 0, which reflects the worst health status.	Baseline and one year follow-up
Subject's Average White Blood Cell Count Over Time	Laboratory analysis of White Blood Cell (WBC) count on blood drawn from subject; WBC fight infection. The normal reference range for WBC count is 4.5 to 10 10^3 cells/microliters. In general, results either lower or higher than the normal range can indicate something is wrong.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Average Red Blood Cell Count Over Time	The red blood cell (RBC) count is a test that measures the number of oxygen-carrying blood cells in your blood. The red blood cell count normal range for women is 4.2 to 5.4 10^6 cells/microliters and for men is 4.7 to 6.1 10^6 cells/microliters. A high red blood cell count may indicate that you have a condition that's preventing you from getting enough oxygen. A low RBC may be caused by an infection, or a medical condition related to anemia. In general, results either lower or higher than the normal range can indicate something is wrong.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Average Hematocrit Percentage Over Time	Laboratory Analysis of Hematocrit Percentage on blood drawn from subjects. A hematocrit test measures the proportion of red blood cells in your blood. Red blood cells carry oxygen throughout your body. Having too few or too many red blood cells can be a sign of certain diseases. Normal hematocrit ranges for adult females are 36% to 44% and for adult males are 41% to 50%. In general, results either lower or higher than the normal range can indicate something is wrong.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Average Hemoglobin Percentage Over Time	Laboratory Analysis of Hemoglobin Count on blood drawn from subjects. Hemoglobin is an oxygen-carrying protein in red blood cells. In males, a healthy hemoglobin level is between 13.2 and 16.6 g/dL. In females, a hemoglobin count of between 11.6 and 15 g/dL is considered normal and healthy. In general, results either lower or higher than the normal range can indicate something is wrong.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up
Subject's Average Plasma Free Hemoglobin Over Time	Laboratory Analysis of Plasma Free Hemoglobin (Hgb) of blood drawn from subject. This blood test measures the level of free hemoglobin in the plasma (liquid portion of the blood). The reference range for plasma free hemoglobin is 0.0 to 15.2 mg/dL. In general, values higher than this can indicate something is wrong.	Discharge, 3 months, 1-, 2-, 3-, 4-, 5-, 6-, 7-, and 8- Years follow-up

Collaborators and Investigators

• Sponsor: Edwards Lifesciences
• Investigators: Principal Investigator: Glenn Barnhart, MD, Swedish Medical Center; Principal Investigator: Walter Randolph Chitwood, MD, East Carolina University

Publications and helpful links

General Publications

• Barnhart GR, Accola KD, Grossi EA, Woo YJ, Mumtaz MA, Sabik JF, Slachman FN, Patel HJ, Borger MA, Garrett HE Jr, Rodriguez E, McCarthy PM, Ryan WH, Duhay FG, Mack MJ, Chitwood WR Jr; TRANSFORM Trial Investigators. TRANSFORM (Multicenter Experience With Rapid Deployment Edwards INTUITY Valve System for Aortic Valve Replacement) US clinical trial: Performance of a rapid deployment aortic valve. J Thorac Cardiovasc Surg. 2017 Feb;153(2):241-251.e2. doi: 10.1016/j.jtcvs.2016.09.062. Epub 2016 Oct 15.
• Romano MA, Koeckert M, Mumtaz MA, Slachman FN, Patel HJ, Chitwood WR Jr, Barnhart GR, Grossi EA; TRANSFORM Trial Investigators. Permanent Pacemaker Implantation After Rapid Deployment Aortic Valve Replacement. Ann Thorac Surg. 2018 Sep;106(3):685-690. doi: 10.1016/j.athoracsur.2018.03.055. Epub 2018 Apr 26.

Helpful Links

• New York Heart Association Classification

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2012
• Primary Completion (Actual): May 26, 2021
• Study Completion (Actual): May 26, 2021

Study Registration Dates

• First Submitted: September 19, 2012
• First Submitted That Met QC Criteria: October 2, 2012
• First Posted (Estimate): October 4, 2012

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Cardiac surgery; Aortic valve; Heart valve; Tissue valve; Bioprosthesis; Valve disorder; Valve disease; Less invasive cardiac surgery; Aortic valve stenosis; Aortic valve regurgitation; Bovine pericardium
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Aortic Valve Insufficiency; Constriction, Pathologic
• Other Study ID Numbers: 2011-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No