Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Medtronic Cardiovascular

ClinicalTrials.gov Identifier:

NCT01240902

First received: November 10, 2010

Last updated: April 27, 2017

Last verified: April 2017

History of Changes

Results First Received: March 6, 2015

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: No masking; Primary Purpose: Treatment
Condition:	Severe Aortic Stenosis
Interventions:	Device: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI) Device: Surgical Aortic Valve Replacement (SAVR)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between Feb 17, 2011 and Aug 23, 2013, 656 subjects were enrolled into the CoreValve US Pivotal Trial Extreme Risk study at 41 of the 43 activated centers in the United States. Between February 2, 2011 and July 23, 2013, 797 subjects were enrolled into the CoreValve US Pivotal Trial High Risk study at 45 centers in the United States.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The first 3 successfully enrolled and implanted iliofemoral subjects at each implanting site, inclusive of both the High Risk Surgical and Extreme Risk patient populations were considered roll-in subjects, and were automatically assigned to undergo Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI).

Reporting Groups

	Description
Extreme Risk: TAVI Iliofemoral	Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access
Extreme Risk: TAVI Non-Iliofemoral	Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access
High Risk: TAVI	High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
High Risk: SAVR	High Risk Surgical Patients: Surgical Aortic Valve Replacement (SAVR)

Participant Flow: Overall Study

	Extreme Risk: TAVI Iliofemoral	Extreme Risk: TAVI Non-Iliofemoral	High Risk: TAVI	High Risk: SAVR
STARTED	500	156	395	402
COMPLETED	289	77	295	237
NOT COMPLETED	211	79	100	165

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participant Population= As Treated (AT) cohort. The AT cohort consisted of all Intent to Treat (ITT) subjects with an attempted implant procedure.

Reporting Groups

	Description
Extreme Risk: TAVI Iliofemoral	Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Iliofemoral Access
Extreme Risk: TAVI Non-Iliofemoral	Extreme Risk Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI); Non-Iliofemoral Access
High Risk: TAVI	High Risk Surgical Patients: Medtronic CoreValve® System Transcatheter Aortic Valve Implantation (TAVI)
High Risk: SAVR	High Risk Surgical Patients: Surgical Aortic Valve Replacement (SAVR)
Total	Total of all reporting groups

Baseline Measures

Extreme Risk: TAVI Iliofemoral

Extreme Risk: TAVI Non-Iliofemoral

High Risk: TAVI

High Risk: SAVR

Total

Overall Participants Analyzed
[Units: Participants]

489

150

391

359

1389

Age ^[1]
[Units: Years]
Mean (Standard Deviation)

83.2 (8.7)

81.3 (7.4)

83.2 (7.1)

83.3 (6.4)

83.0 (7.6)

^[1]	Participant Population= Consisted of all subjects with an attempted implant procedure.

Sex: Female, Male ^[1]
[Units: Participants]
Count of Participants

Female

255 52.1%

82 54.7%

184 47.1%

171 47.6%

692 49.8%

Male

234 47.9%

68 45.3%

207 52.9%

188 52.4%

697 50.2%

^[1]	Participant Population= Consisted of all subjects with an attempted implant procedure.

Race/Ethnicity, Customized ^[1]
[Units: Participants]

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

468

143

387

343

1341

More than one race

Unknown or Not Reported

^[1]	Participant Population= Consisted of all subjects with an attempted implant procedure.

Body Surface Area ^[1]
[Units: M^2]
Mean (Standard Deviation)

1.8 (0.3)

1.8 (0.2)

1.9 (0.2)

1.8 (0.2)

^[1]	Participant Population= Consisted of all subjects with an attempted implant procedure.

NYHA Classification ^[1]
[Units: Participants]

NYHA I

NYHA II

156

NYHA III

313

255

250

916

NYHA IV

136

317

^[1]

New York Heart Association (NYHA) Classification:

Class I: Subjects with cardiac disease but without resulting limitations of physical activity.

Class I: Subjects with cardiac disease resulting in slight limitation of physical activity.

Class III: Subjects with cardiac disease resulting in marked limitation of physical activity.

Class IV: Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort.

Society of Thoracic Surgeons (STS) Risk Score ^[1]
[Units: % risk of mortality or morbidity]
Mean (Standard Deviation)

10.3 (5.5)

10.7 (5.7)

7.3 (3.0)

7.5 (3.3)

8.8 (4.7)

^[1]

The Society of Thoracic Surgeons (STS) risk model predicts the risk of operative mortality and morbidity after adult cardiac surgery on the basis of patient demographic and clinical variables. After information has been entered on a given case, the online STS risk calculator provides a risk percentage for each of the outcomes. The risk percentage estimates the chance of a specific outcome for a patient with the indicated risk factors. A higher score indicates a higher risk. A lower score indicates a lower risk.

Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) ^[1]
[Units: %]
Mean (Standard Deviation)

22.6 (17.1)

22.9 (15.9)

17.7 (13.0)

18.8 (13.2)

20.3 (15.1)

^[1]	The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is a method of calculating predicted operative mortality for patients undergoing cardiac surgery. If a risk factor is present, a weight/number is assigned. The weights are added to give an approximate percent of predicted mortality. A higher score indicates a higher risk. A lower score indicates a lower risk.

Outcome Measures

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1. Primary:

Extreme Risk: All-cause Death or Major Stroke; High Risk Surgical: All-cause Mortality [ Time Frame: 1 year ]

Show Outcome Measure 1

2. Secondary:

Major Adverse Cardiovascular and Cerebrovascular Event (MACCE) [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 2

3. Secondary:

The Occurrence of Individual MACCE Components [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

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4. Secondary:

Major Adverse Events (MAEs) [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

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5. Secondary:

Conduction Disturbance Requiring Permanent Pacemaker Implantation [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 5

6. Secondary:

Change in NYHA Class [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 6

7. Secondary:

Change in Distance Walked During 6-Minute Walk Test (6MWT) [ Time Frame: 30 day, 1 year ]

Show Outcome Measure 7

8. Secondary:

Ratio of Days Alive Out of Hospital Versus Total Days Alive [ Time Frame: 1 year ]

Show Outcome Measure 8

9. Secondary:

Quality of Life (QoL) Change [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 9

10. Secondary:

Echocardiographic Assessment of Valve Performance [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 10

11. Secondary:

Echocardiographic Assessment of Valve Performance [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 11

12. Secondary:

Echocardiographic Assessment of Valve Performance [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 12

13. Secondary:

Aortic Valve Hospitalizations [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 13

14. Secondary:

Cardiovascular Deaths and Valve Related Deaths [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 14

15. Secondary:

Strokes and Transient Ischemic Attacks (TIAs) [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 15

16. Secondary:

Index Procedure Related MAEs [ Time Frame: Procedure ]

Show Outcome Measure 16

17. Secondary:

Length of Index Procedure Hospital Stay [ Time Frame: Number of days from admission to discharge ]

Show Outcome Measure 17

18. Secondary:

Device Success [ Time Frame: Number of days from admission to discharge ]

Show Outcome Measure 18

19. Secondary:

Procedural Success [ Time Frame: Number of days from admission to discharge ]

Show Outcome Measure 19

20. Secondary:

Prosthetic Valve Dysfunction (PVD) [ Time Frame: 30 day, 6 month, 1 year, 2 year ]

Show Outcome Measure 20

Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Results Point of Contact:

Name/Title: Hatice Bilgic Lim
Organization: Medtronic, Inc.
e-mail: rs.medtroniccardiovascularclinicaltrials@medtronic.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kleiman NS, Maini BJ, Reardon MJ, Conte J, Katz S, Rajagopal V, Kauten J, Hartman A, McKay R, Hagberg R, Huang J, Popma J; CoreValve Investigators. Neurological Events Following Transcatheter Aortic Valve Replacement and Their Predictors: A Report From the CoreValve Trials. Circ Cardiovasc Interv. 2016 Sep;9(9). pii: e003551. doi: 10.1161/CIRCINTERVENTIONS.115.003551.

Reardon MJ, Kleiman NS, Adams DH, Yakubov SJ, Coselli JS, Deeb GM, O'Hair D, Gleason TG, Lee JS, Hermiller JB Jr, Chetcuti S, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Maini B, Mumtaz M, Conte JV, Resar JR, Aharonian V, Pfeffer T, Oh JK, Huang J, Popma JJ. Outcomes in the Randomized CoreValve US Pivotal High Risk Trial in Patients With a Society of Thoracic Surgeons Risk Score of 7% or Less. JAMA Cardiol. 2016 Nov 1;1(8):945-949. doi: 10.1001/jamacardio.2016.2257.

Popma JJ, Reardon MJ, Yakubov SJ, Hermiller JB Jr, Harrison JK, Gleason TG, Conte JV, Deeb GM, Chetcuti S, Oh JK, Boulware MJ, Huang J, Adams DH; CoreValve US Clinical Investigators. Safety and Efficacy of Self-Expanding TAVR in Patients With Aortoventricular Angulation. JACC Cardiovasc Imaging. 2016 Aug;9(8):973-81. doi: 10.1016/j.jcmg.2016.06.002.

Hermiller JB Jr, Yakubov SJ, Reardon MJ, Deeb GM, Adams DH, Afilalo J, Huang J, Popma JJ; CoreValve United States Clinical Investigators. Predicting Early and Late Mortality After Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2016 Jul 26;68(4):343-52. doi: 10.1016/j.jacc.2016.04.057.

Popma JJ, Gleason TG, Yakubov SJ, Harrison JK, Forrest JK, Maini B, Ruiz CE, Pinto DS, Costa M, Resar J, Conte J, Crestanello J, Chang Y, Oh JK, Reardon MJ, Adams DH. Relationship of Annular Sizing Using Multidetector Computed Tomographic Imaging and Clinical Outcomes After Self-Expanding CoreValve Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 2016 Jul;9(7). pii: e003282. doi: 10.1161/CIRCINTERVENTIONS.115.003282.

Little SH, Oh JK, Gillam L, Sengupta PP, Orsinelli DA, Cavalcante JL, Chang JD, Adams DH, Zorn GL 3rd, Pollak AW, Abdelmoneim SS, Reardon MJ, Qiao H, Popma JJ. Self-Expanding Transcatheter Aortic Valve Replacement Versus Surgical Valve Replacement in Patients at High Risk for Surgery: A Study of Echocardiographic Change and Risk Prediction. Circ Cardiovasc Interv. 2016 Jun;9(6). pii: e003426. doi: 10.1161/CIRCINTERVENTIONS.115.003426.

Dauerman HL, Reardon MJ, Popma JJ, Little SH, Cavalcante JL, Adams DH, Kleiman NS, Oh JK. Early Recovery of Left Ventricular Systolic Function After CoreValve Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 2016 Jun;9(6). pii: e003425. doi: 10.1161/CIRCINTERVENTIONS.115.003425.

Deeb GM, Reardon MJ, Chetcuti S, Patel HJ, Grossman PM, Yakubov SJ, Kleiman NS, Coselli JS, Gleason TG, Lee JS, Hermiller JB Jr, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Maini B, Mumtaz M, Conte J, Resar J, Aharonian V, Pfeffer T, Oh JK, Qiao H, Adams DH, Popma JJ; CoreValve US Clinical Investigators. 3-Year Outcomes in High-Risk Patients Who Underwent Surgical or Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2016 Jun 7;67(22):2565-74. doi: 10.1016/j.jacc.2016.03.506. Epub 2016 Apr 3.

Reynolds MR, Lei Y, Wang K, Chinnakondepalli K, Vilain KA, Magnuson EA, Galper BZ, Meduri CU, Arnold SV, Baron SJ, Reardon MJ, Adams DH, Popma JJ, Cohen DJ; CoreValve US High Risk Pivotal Trial Investigators. Cost-Effectiveness of Transcatheter Aortic Valve Replacement With a Self-Expanding Prosthesis Versus Surgical Aortic Valve Replacement. J Am Coll Cardiol. 2016 Jan 5;67(1):29-38. doi: 10.1016/j.jacc.2015.10.046.

Oh JK, Little SH, Abdelmoneim SS, Reardon MJ, Kleiman NS, Lin G, Bach D, Gillam L, Kar B, Coselli J, Sengupta PP, Grewal K, Chang J, Chang Y, Boulware M, Adams DH, Popma JJ; CoreValve U.S. Pivotal Trial Clinical Investigators. Regression of Paravalvular Aortic Regurgitation and Remodeling of Self-Expanding Transcatheter Aortic Valve: An Observation From the CoreValve U.S. Pivotal Trial. JACC Cardiovasc Imaging. 2015 Dec;8(12):1364-75. doi: 10.1016/j.jcmg.2015.07.012. Epub 2015 Oct 26.

Yakubov SJ, Adams DH, Watson DR, Reardon MJ, Kleiman NS, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Coselli J, Diez J, Schreiber T, Gleason TG, Conte J, Deeb GM, Huang J, Oh J, Byrne T, Caskey M, Popma JJ; CoreValve United States Clinical Investigators. 2-Year Outcomes After Iliofemoral Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery. J Am Coll Cardiol. 2015 Sep 22;66(12):1327-34. doi: 10.1016/j.jacc.2015.07.042.

Arnold SV, Reynolds MR, Wang K, Magnuson EA, Baron SJ, Chinnakondepalli KM, Reardon MJ, Tadros PN, Zorn GL, Maini B, Mumtaz MA, Brown JM, Kipperman RM, Adams DH, Popma JJ, Cohen DJ; CoreValve US Pivotal Trial Investigators. Health Status After Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Increased Surgical Risk: Results From the CoreValve US Pivotal Trial. JACC Cardiovasc Interv. 2015 Aug 17;8(9):1207-17. doi: 10.1016/j.jcin.2015.04.018.

Reardon MJ, Adams DH, Kleiman NS, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Lee JS, Hermiller JB Jr, Chetcuti S, Heiser J, Merhi W, Zorn GL 3rd, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Maini B, Mumtaz M, Conte JV, Resar JR, Aharonian V, Pfeffer T, Oh JK, Qiao H, Popma JJ. 2-Year Outcomes in Patients Undergoing Surgical or Self-Expanding Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2015 Jul 14;66(2):113-21. doi: 10.1016/j.jacc.2015.05.017. Epub 2015 Jun 5.

Osnabrugge RL, Arnold SV, Reynolds MR, Magnuson EA, Wang K, Gaudiani VA, Stoler RC, Burdon TA, Kleiman N, Reardon MJ, Adams DH, Popma JJ, Cohen DJ; CoreValve U.S. Trial Investigators. Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve U.S. trial. JACC Cardiovasc Interv. 2015 Feb;8(2):315-23. doi: 10.1016/j.jcin.2014.08.016.

Reardon MJ, Adams DH, Coselli JS, Deeb GM, Kleiman NS, Chetcuti S, Yakubov SJ, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Khabbaz K, Tadros P, Zorn GL 3rd, Merhi W, Heiser J, Petrossian G, Robinson N, Maini B, Mumtaz M, Lee JS, Gleason TG, Resar J, Conte J, Watson D, Chenoweth S, Popma JJ; CoreValve US Clinical Investigators. Self-expanding transcatheter aortic valve replacement using alternative access sites in symptomatic patients with severe aortic stenosis deemed extreme risk of surgery. J Thorac Cardiovasc Surg. 2014 Dec;148(6):2869-76.e1-7. doi: 10.1016/j.jtcvs.2014.07.020. Epub 2014 Jul 30.

Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J Jr, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S, Oh JK; U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 May 8;370(19):1790-8. doi: 10.1056/NEJMoa1400590. Epub 2014 Mar 29.

Popma JJ, Adams DH, Reardon MJ, Yakubov SJ, Kleiman NS, Heimansohn D, Hermiller J Jr, Hughes GC, Harrison JK, Coselli J, Diez J, Kafi A, Schreiber T, Gleason TG, Conte J, Buchbinder M, Deeb GM, Carabello B, Serruys PW, Chenoweth S, Oh JK; CoreValve United States Clinical Investigators. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol. 2014 May 20;63(19):1972-81. doi: 10.1016/j.jacc.2014.02.556. Epub 2014 Mar 19.

Responsible Party:	Medtronic Cardiovascular
ClinicalTrials.gov Identifier:	NCT01240902 History of Changes
Other Study ID Numbers:	MCV-US-2009-01
Study First Received:	November 10, 2010
Results First Received:	March 6, 2015
Last Updated:	April 27, 2017

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