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

• ClinicalTrials.gov Identifier: NCT01700439
• Recruitment Status: Active, not recruiting
• First Posted: October 4, 2012
• Results First Posted: December 13, 2017
• Last Update Posted: March 30, 2020
• Sponsor: Edwards Lifesciences
• Information provided by (Responsible Party): Edwards Lifesciences

Tracking Information

• First Submitted Date: September 19, 2012
• First Posted Date: October 4, 2012
• Results First Submitted Date: September 22, 2017
• Results First Posted Date: December 13, 2017
• Last Update Posted Date: March 30, 2020
• Study Start Date: September 2012
• Actual Primary Completion Date: August 12, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 12, 2017)

Number of Late Adverse Events Divided by Late Patient Years (Expressed as a Percentage) [ Time Frame: Events occurring ≥ 31 days and up through 2 years post-implant ]

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]

Original Primary Outcome Measures (submitted: October 2, 2012)

Long term Performance: Clinically acceptable function by echocardiogram [ Time Frame: All subjects will be assessed for clinical follow-up at the following intervals: Discharge, 1 mo., 3 mo., 1 yr and annually thereafter thru 5 yr follow-up per subject. ]

The safety endpoints consist of mortality, valve thrombosis, thromboembolism, hemorrhage, paravalvular leak, endocarditis, structural and non-structural valve deterioration, explant, hemolysis, re-operation, and implant related new or worsening of a cardiac conduction issue.

Current Secondary Outcome Measures (submitted: December 12, 2017)

• Percentage of Subjects With Edwards INTUITY Surgical Aortic Heart Valve Device Technical Success [ Time Frame: Day of procedure ]
  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.
• Percentage of Subjects With Edwards INTUITY Surgical Heart Valve Procedural Success [ Time Frame: Day of procedure through discharge or 10 days post index procedure, whichever comes first. ]
  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.
• Average Amount of Time Subject Spent on Cardiopulmonary Bypass [ Time Frame: Day of procedure ]
  Surgical and hospitalization factors - Cardiopulmonary bypass time
• Average Subject Time on Cardiopulmonary Cross Clamp [ Time Frame: Day of procedure ]
  Surgical and hospitalization factors - Cardiopulmonary cross clamp time
• Average Number of Days Subjects Were in the Intensive Care Unit (ICU) [ Time Frame: Day of procedure through discharge from the hospital ]
  Length of time surgical subjects were in the intensive care unit (ICU) after their heart valve replacement procedure.
• Subject's Percentage of Change at 1 Year From Baseline in New York Heart Association (NYHA) Class [ Time Frame: Baseline and one year follow-up ]
  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.
• Subject's Average Gradient Measurements at 1 Year [ Time Frame: 1 Year follow-up ]
  Hemodynamic performance - Mean and peak gradients evaluated by echocardiography
• Subject's Effective Orifice Area (EOA) Measurement at 1 Year [ Time Frame: 1 Year follow-up ]
  Hemodynamic performance - Effective Orifice Area (EOA) evaluated by echocardiography
• Subject's Effective Orifice Area Index (EOAI) Measurement at 1 Year [ Time Frame: 1 year follow-up ]
  Hemodynamic performance - Effective Orifice Area Index evaluated by echocardiography
• Subject's Performance Index Measurement at 1 Year [ Time Frame: 1 Year follow-up ]
  Hemodynamic performance - Performance Index evaluated by echocardiography
• Subject's Cardiac Output Measurement at 1 Year [ Time Frame: 1 Year follow-up ]
  Hemodynamic performance - Cardiac Output evaluated by echocardiography
• Subject's Cardiac Index Measurement at 1 Year [ Time Frame: 1 Year follow-up ]
  Hemodynamic performance - Cardiac index evaluated by echocardiography
• Amount of Aortic Valvular Regurgitation in Subjects at 1 Year by Valve Size [ Time Frame: 1 Year follow-up ]
  Hemodynamic performance - Aortic valvular regurgitation evaluated by echocardiography

Original Secondary Outcome Measures (submitted: October 2, 2012)

Hemodynamic performance assessed by echocardiogram [ Time Frame: All subjects will be assessed for clinical follow-up at the following intervals: Discharge, 1 mo., 3 mo., 1 yr and annually thereafter thru 5 yr follow-up per subject. ]

Effectiveness endpoints consists of device technical success, cross-clamp time, cardiopulmonary bypass time, length of time in the intensive care unit, NYHA functional class compared to baseline, and hemodynamic performance of the heart valve device confirmed by echocardiography.

Current Other Pre-specified Outcome Measures (submitted: December 12, 2017)

• Subject's Average Score at Baseline and 1 Year on the Quality of Life Survey [ Time Frame: Baseline and one year follow-up ]
  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.
• Subject's Average White Blood Cell Count at 1 Year [ Time Frame: 1 Year follow-up ]
  Laboratory analysis of White Blood Cell Count on blood drawn from subject.
• Subject's Average Red Blood Cell Count at 1 Year [ Time Frame: 1 Year follow-up ]
  Laboratory analysis of Red Blood Cell Count of blood drawn from subject.
• Subject's Average Hematocrit Percentage at 1 Year [ Time Frame: 1 Year follow-up ]
  Laboratory analysis of Hematocrit of blood drawn from subject.
• Subject's Average Hemoglobin Percentage at 1 Year [ Time Frame: 1 Year follow-up ]
  Laboratory analysis of Hemoglobin of blood drawn from subject.
• Subject's Average Plasma Free Hemoglobin at 1 Year [ Time Frame: 1 Year follow-up ]
  Laboratory Analysis of Plasma Free Hemoglobin of blood drawn from subject.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Surgical Treatment of Aortic Stenosis With a Next Generation, Rapid Deployment Surgical Aortic Valve
• Official Title: Multi-CenTer Experience With the Rapid Deployment EDWARDS INTUITY Valve System FOR Aortic Valve ReplaceMent
• Brief Summary: The purpose of the clinical study is to prove that the heart valve device is safe, effective, and performs as intended.
• 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
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Aortic Valve Stenosis
• Aortic Valve Stenosis With Insufficiency
• Regurgitation, Aortic Valve
• Aortic Valve Incompetence

Intervention

Device: EDWARDS INTUITY valve

Surgical replacement of the aortic valve with the EDWARDS INTUITY valve.

Study Arms

Experimental: EDWARDS INTUITY valve

All subjects enrolled into the study are implanted with the EDWARDS INTUITY Valve System.

Intervention: Device: EDWARDS INTUITY valve

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 12, 2017): 934
• Original Estimated Enrollment (submitted: October 2, 2012): 650
• Estimated Study Completion Date: November 2021
• Actual Primary Completion Date: August 12, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 replace-ment 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01700439
• Other Study ID Numbers: 2011-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Responsible Party: Edwards Lifesciences
• Study Sponsor: Edwards Lifesciences
• Collaborators: Not Provided

Investigators

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

• PRS Account: Edwards Lifesciences
• Verification Date: March 2020