Surgical Treatment of Aortic Stenosis With a Next Generation, Rapid Deployment Surgical Aortic Valve

Aortic Valve Stenosis Clinical Trial

— TRANSFORM™  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01700439
• Other study ID #: 2011-02
• Status: Completed
• Phase: N/A
• Start date: September 26, 2012
• Est. completion date: May 26, 2021

Study information

• Verified date: May 2023
• Source: Edwards Lifesciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 934
• Est. completion date: May 26, 2021
• Est. primary completion date: May 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Device:
• EDWARDS INTUITY valve
Surgical replacement of the aortic valve with the EDWARDS INTUITY valve.

Locations

Country	Name	City	State
United States	The University of Michigan Medical School	Ann Arbor	Michigan
United States	Mission Hospital	Asheville	North Carolina
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Cooper University Hospital	Camden	New Jersey
United States	Northwestern University	Chicago	Illinois
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Pinnacle Health at Harrisburg Hospital	Harrisburg	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Keck Hospital of University of Southern California	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	North Shore Long Island Jewish Health System	Manhasset	New York
United States	Baptist Memorial Hospital	Memphis	Tennessee
United States	Aurora St Luke's Medical Center	Milwaukee	Wisconsin
United States	St. Thomas Health	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	New York University Medical Center	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Florida Hospital	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	The Heart Hospital Baylor Plano	Plano	Texas
United States	Mercy General Hospital	Sacramento	California
United States	Washington University - Barnes Jewish Hospital	Saint Louis	Missouri
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Edwards Lifesciences

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 Ra — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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.
Secondary	Average Amount of Time Subject Spent on Cardiopulmonary Bypass	Surgical and hospitalization factors - Cardiopulmonary bypass time	Day of procedure
Secondary	Average Subject Time on Cardiopulmonary Cross Clamp	Surgical and hospitalization factors - Cardiopulmonary cross clamp time	Day of procedure
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   New York Heart Association Classification