Pivotal Study of a Percutaneous Mitral Valve Repair System (EVEREST II) - Full Text View

Sponsor:	Evalve
Information provided by:	Evalve
ClinicalTrials.gov Identifier:	NCT00209274

Purpose

Prospective, multi-center, randomized study of the Evalve Inc., Cardiovascular Valve Repair System (MitraClip® implant) in the treatment of mitral valve regurgitation. Patients will undergo 30-day, 6-month and 12-month clinical follow-up of the primary endpoints, and then annually for up to 5 years post procedure.

Condition	Intervention	Phase
Mitral Valve Insufficiency Mitral Valve Regurgitation Mitral Valve Incompetence Mitral Regurgitation Mitral Insufficiency	Device: Percutaneous mitral valve repair using MitraClip implant Procedure: Mitral valve repair or replacement surgery	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Pivotal Study: A Study of the Evalve Cardiovascular Valve Repair System - Endovascular Valve Edge-to-Edge REpair STudy (EVEREST II) and Real World ExpAnded MuLtIcenter Study of the MitraClip System (REALISM).

Further study details as provided by Evalve:

Primary Outcome Measures:

Freedom from surgery for valve dysfunction, death, and moderate to severe (3+) or severe (4+) mitral regurgitation at 12 months. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Freedom from major adverse events (MAE) at 30 days or hospital discharge, whichever is longer. [ Time Frame: 30 days or hospital discharge, whichever is longer ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Non-cerebral thromboembolism [ Time Frame: 30 days or hospital discharge, whichever is longer and 12 months. ] [ Designated as safety issue: Yes ]
Occurrence of endocarditis [ Time Frame: 30 days or hospital discharge, whichever is longer at 12 months ] [ Designated as safety issue: Yes ]
Occurrence of thrombosis [ Time Frame: 30 days or hospital discharge, whichever is longer at 12 months ] [ Designated as safety issue: Yes ]
Occurrence of hemolysis [ Time Frame: 30 days or hospital discharge, whichever is longer at 12 months ] [ Designated as safety issue: Yes ]
Occurrence of clinically significant Atrial septal defect [ Time Frame: 30 days or hospital discharge, whichever is longer at 12 months ] [ Designated as safety issue: Yes ]
MV stenosis [ Time Frame: 30 days or hospital discharge, whichever is longer at 12 months ] [ Designated as safety issue: Yes ]
NYHA functional class [ Time Frame: 30 days or hospital discharge, whichever is longer at 12 months ] [ Designated as safety issue: Yes ]
Acute procedural success defined as successful MitraClip implantation with resulting MR of 2+ or less [ Time Frame: Discharge ] [ Designated as safety issue: No ]
Post-procedure length of hospital stay [ Time Frame: Discharge ] [ Designated as safety issue: No ]
Quality of Life [ Time Frame: 30 days and 12 months ] [ Designated as safety issue: No ]
Major vascular and bleeding complications [ Time Frame: 30 days or hospital discharge, whichever is longer and 12 months ] [ Designated as safety issue: Yes ]
Occurrence of MAE [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Occurrence of dysrhythmias [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Occurrence of MAE in patients over 75 years of age [ Time Frame: 30 days or hospital discharge, whichever is longer and 12 months ] [ Designated as safety issue: Yes ]
Mitral valve repair success [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Effectiveness at 18 and 24 months [ Time Frame: 18 and 24 months ] [ Designated as safety issue: No ]
Estimation of durability (Bayesian Analysis) [ Time Frame: 18 and 24 months ] [ Designated as safety issue: No ]
Clip implant rate defined as the rate of successful implantation of MitraClip(s) [ Time Frame: procedural ] [ Designated as safety issue: No ]
Procedural freedom from MAE [ Time Frame: procedural ] [ Designated as safety issue: Yes ]
Acute surgical success defined as successful mitral valve repair or replacement [ Time Frame: Discharge ] [ Designated as safety issue: No ]
Left ventricular status [ Time Frame: 30 days or hospital discharge,whichever is longer and 12 months ] [ Designated as safety issue: No ]
Hospital readmission [ Time Frame: 30 days or hospital discharge, whichever is longer and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	957
Study Start Date:	May 2005
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Percutaneous mitral valve repair using MitraClip implant.	Device: Percutaneous mitral valve repair using MitraClip implant MitraClip Implant Other Name: MitraClip
Active Comparator: 2 Mitral valve repair or replacement surgery.	Procedure: Mitral valve repair or replacement surgery Repair or replacement of mitral valve

Detailed Description:

Prospective, multi-center, randomized study of the safety and effectiveness of an endovascular approach to the treatment of mitral valve regurgitation using the Evalve Cardiovascular Valve Repair System (MitraClip® implant).

A minimum of 258 evaluable patients randomized 2:1 to the study and control arms, respectively, are required to test the primary safety and effectiveness endpoints. In addition, up to 111 randomized roll-ins, 87 high risk patients, and 120 continued access patients may be enrolled.

Up to 47 clinical sites throughout the US and Canada may participate. Only US sites are participating in REALISM.

The study is powered to show non-inferiority of effectiveness of an endovascular treatment strategy with the MitraClip as compared to a treatment strategy of mitral valve repair or replacement surgery. The primary efficacy endpoint is freedom from: surgery for Valve Dysfunction, death, and MR > 2+ (moderate to severe (3+) or severe (4+) mitral regurgitation) at 12 months.

The study is powered to show superiority of safety at 30 days of an endovascular treatment strategy with the Clip as compared to a treatment strategy of mitral valve repair or replacement surgery.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion/Exclusion Criteria:

Patients who have been diagnosed with Grade 3 (moderate to severe) or Grade 4 (severe) mitral regurgitation (MR), who are seeking treatment for their condition and who at least:

Symptomatic
If asymptomatic, must have evidence of left ventricular dysfunction
Are 18 years or older.
Are candidates for mitral valve surgery.
Do not have an active peptic uler (a hole in the lining of the stomach, the duodenum - first part of the small intestine - or the esophagus, the tube that connects the throat to the stomach), nor have experienced bleeding in the upper gastro-intestinal tract, within the last six months.
Do not require dialysis (process of cleansing the blood, by passing it through a machine).
Do not have a history of intravenous drug abuse (drugs injected into the veins).
Do not have allergies or hypersensitivity to aspirin, heparin (anti-blood-clotting medication), Ticlid (anti-blood-clotting medication) , Plavix (anti-blood-clotting medication), or contrast media (dye used in X-rays).
Appropriate valve anatomy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00209274

Contacts

Contact: Jill A Hannemann	650-833-1654	jill.hannemann@av.abbott.com
Contact: Chrysbe D Madayag	650-833-1650	chrysbe.madayag@av.abbott.com

Locations

United States, Illinois
Evanston Northwestern Healthcare	Recruiting
Evanston, Illinois, United States, 60201
Principal Investigator: Ted E Feldman, MD

Sponsors and Collaborators

Evalve

Investigators

Principal Investigator:	Ted Feldman, M.D.	NorthShore University HealthSystem Research Institute
Principal Investigator:	Donald G Glower Jr., MD	Duke University Medical Center, Department of Surgery

More Information

Additional Information:

Web site listing study sites and describing mitral regurgitation, symptoms, clinical consequences and treatments This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

Dang NC, Aboodi MS, Sakaguchi T, Wasserman HS, Argenziano M, Cosgrove DM, Rosengart TK, Feldman T, Block PC, Oz MC. Surgical revision after percutaneous mitral valve repair with a clip: initial multicenter experience. Ann Thorac Surg. 2005 Dec;80(6):2338-42.

Feldman T, Wasserman HS, Herrmann HC, Gray W, Block PC, Whitlow P, St Goar F, Rodriguez L, Silvestry F, Schwartz A, Sanborn TA, Condado JA, Foster E. Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol. 2005 Dec 6;46(11):2134-40. Epub 2005 Oct 19.

Herrmann HC, Rohatgi S, Wasserman HS, Block P, Gray W, Hamilton A, Zunamon A, Homma S, Di Tullio MR, Kraybill K, Merlino J, Martin R, Rodriguez L, Stewart WJ, Whitlow P, Wiegers SE, Silvestry FE, Foster E, Feldman T. Mitral valve hemodynamic effects of percutaneous edge-to-edge repair with the MitraClip device for mitral regurgitation. Catheter Cardiovasc Interv. 2006 Dec;68(6):821-8.

Luk A, Butany J, Ahn E, Fann JI, St Goar F, Thornton T, McDermott L, Madayag C, Komtebedde J. Mitral repair with the Evalve MitraClip device: histopathologic findings in the porcine model. Cardiovasc Pathol. 2008 Aug 12; [Epub ahead of print]

Silvestry FE, Rodriguez LL, Herrmann HC, Rohatgi S, Weiss SJ, Stewart WJ, Homma S, Goyal N, Pulerwitz T, Zunamon A, Hamilton A, Merlino J, Martin R, Krabill K, Block PC, Whitlow P, Tuzcu EM, Kapadia S, Gray WA, Reisman M, Wasserman H, Schwartz A, Foster E, Feldman T, Wiegers SE. Echocardiographic guidance and assessment of percutaneous repair for mitral regurgitation with the Evalve MitraClip: lessons learned from EVEREST I. J Am Soc Echocardiogr. 2007 Oct;20(10):1131-40. Epub 2007 Jun 13.

Mauri L, Garg P, Massaro JM, Foster E, Glower D, Mehoudar P, Powell F, Komtebedde J, McDermott E, Feldman T. The EVEREST II Trial: design and rationale for a randomized study of the evalve mitraclip system compared with mitral valve surgery for mitral regurgitation. Am Heart J. 2010 Jul;160(1):23-9.

Fann JI, St Goar FG, Komtebedde J, Oz MC, Block PC, Foster E, Butany J, Feldman T, Burdon TA. Beating heart catheter-based edge-to-edge mitral valve procedure in a porcine model: efficacy and healing response. Circulation. 2004 Aug 24;110(8):988-93. Epub 2004 Aug 9.

St Goar FG, Fann JI, Komtebedde J, Foster E, Oz MC, Fogarty TJ, Feldman T, Block PC. Endovascular edge-to-edge mitral valve repair: short-term results in a porcine model. Circulation. 2003 Oct 21;108(16):1990-3. Epub 2003 Oct 6.

Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; 2006 Writing Committee Members; American College of Cardiology/American Heart Association Task Force. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008 Oct 7;118(15):e523-661. Epub 2008 Sep 26. No abstract available.

Borgia F, Di Mario C, Franzen O. Adenosine-induced asystole to facilitate MitraClip placement in a patient with adverse mitral valve morphology. Heart. 2010 Oct 29; [Epub ahead of print] No abstract available.

Tamburino C, Immè S, Barbanti M, Mulè M, Pistritto AM, Aruta P, Cammalleri V, Scarabelli M, Mangiafico S, Scandura S, Ussia GP. Reduction of mitral valve regurgitation with Mitraclip percutaneous system. Minerva Cardioangiol. 2010 Oct;58(5):589-98.

Ciobanu A, Bennett S, Azam M, Clark A, Vinereanu D. Incremental value of three-dimensional transoesophageal echocardiography for guiding double percutaneous MitraClip(R) implantation in a 'no option' patient. Eur J Echocardiogr. 2010 Sep 27; [Epub ahead of print]

Lim DS, Kunjummen BJ, Smalling R. Mitral valve repair with the MitraClip device after prior surgical mitral annuloplasty. Catheter Cardiovasc Interv. 2010 Sep 1;76(3):455-9.

Kalarus Z, Kukulski T, Lekston A, Streb W, Sikora J, Nadziakiewicz P, Gasior M, Polo?ski L, Zembala M. [Methodology and safety of transvascular reduction of severe ischaemic mitral insufficiency with MitraClip in high-surgical-risk patients - first three cases in Poland]. Kardiol Pol. 2010 Jun;68(6):729-35. Polish.

Geidel S, Ostermeyer J, Lass M, Schmoeckel M. Complex surgical valve repair after failed percutaneous mitral intervention using the MitraClip device. Ann Thorac Surg. 2010 Jul;90(1):277-9.

Jönsson A, Settergren M. MitraClip catheter-based mitral valve repair system. Expert Rev Med Devices. 2010 Jul;7(4):439-47.

Ussia GP, Barbanti M, Tamburino C. Feasibility of percutaneous transcatheter mitral valve repair with the MitraClip system using conscious sedation. Catheter Cardiovasc Interv. 2010 Jun 1;75(7):1137-40.

Tamburino C, Ussia GP, Maisano F, Capodanno D, La Canna G, Scandura S, Colombo A, Giacomini A, Michev I, Mangiafico S, Cammalleri V, Barbanti M, Alfieri O. Percutaneous mitral valve repair with the MitraClip system: acute results from a real world setting. Eur Heart J. 2010 Jun;31(11):1382-9. Epub 2010 Mar 18.

Franzen O, Baldus S, Rudolph V, Meyer S, Knap M, Koschyk D, Treede H, Barmeyer A, Schofer J, Costard-Jäckle A, Schlüter M, Reichenspurner H, Meinertz T. Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. 2010 Jun;31(11):1373-81. Epub 2010 Mar 10.

Argenziano M, Skipper E, Heimansohn D, Letsou GV, Woo YJ, Kron I, Alexander J, Cleveland J, Kong B, Davidson M, Vassiliades T, Krieger K, Sako E, Tibi P, Galloway A, Foster E, Feldman T, Glower D; EVEREST Investigators. Surgical revision after percutaneous mitral repair with the MitraClip device. Ann Thorac Surg. 2010 Jan;89(1):72-80; discussion p 80.

Rogers JH, Yeo KK, Carroll JD, Cleveland J, Reece TB, Gillinov AM, Rodriguez L, Whitlow P, Woo YJ, Herrmann HC, Young JN. Late surgical mitral valve repair after percutaneous repair with the MitraClip system. J Card Surg. 2009 Nov-Dec;24(6):677-81. Epub 2009 Jul 24.

Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, Whitlow PL, Gray W, Low R, Herrmann HC, Lim S, Foster E, Glower D; EVEREST Investigators. Percutaneous mitral repair with the MitraClip system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair Study) Cohort. J Am Coll Cardiol. 2009 Aug 18;54(8):686-94.

Herrmann HC, Kar S, Siegel R, Fail P, Loghin C, Lim S, Hahn R, Rogers JH, Bommer WJ, Wang A, Berke A, Lerakis S, Kramer P, Wong SC, Foster E, Glower D, Feldman T; EVEREST Investigators. Effect of percutaneous mitral repair with the MitraClip device on mitral valve area and gradient. EuroIntervention. 2009 Jan;4(4):437-42.

Luk A, Butany J, Ahn E, Fann JI, St Goar F, Thornton T, McDermott L, Madayag C, Komtebedde J. Mitral repair with the Evalve MitraClip device: histopathologic findings in the porcine model. Cardiovasc Pathol. 2008 Aug 12; [Epub ahead of print]

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

Siegel RJ, Biner S, Rafique AM, Rinaldi M, Lim S, Fail P, Hermiller J, Smalling R, Whitlow PL, Herrmann HC, Foster E, Feldman T, Glower D, Kar S; EVEREST Investigators. The acute hemodynamic effects of MitraClip therapy. J Am Coll Cardiol. 2011 Apr 19;57(16):1658-65.

Feldman T, Foster E, Glower DG, Kar S, Rinaldi MJ, Fail PS, Smalling RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T, Letsou GV, Massaro JM, Mauri L; EVEREST II Investigators. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011 Apr 14;364(15):1395-406. Epub 2011 Apr 4.

Ladich E, Michaels MB, Jones RM, McDermott E, Coleman L, Komtebedde J, Glower D, Argenziano M, Feldman T, Nakano M, Virmani R; Endovascular Valve Edge-to-Edge Repair Study (EVEREST) Investigators. Pathological healing response of explanted MitraClip devices. Circulation. 2011 Apr 5;123(13):1418-27. Epub 2011 Mar 21.

Responsible Party:	Elizabeth McDermott, Divisional Vice President of Regulatory and Clinical Affairs, Abbott Vascular Structural Heart (Evalve Inc)
ClinicalTrials.gov Identifier:	NCT00209274 History of Changes
Other Study ID Numbers:	Protocol #0401, Protocol #0401
Study First Received:	September 13, 2005
Last Updated:	February 1, 2011
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada

Keywords provided by Evalve:

Mitral Valve Insufficiency
Mitral Valve Regurgitation
Mitral Valve Incompetence
Mitral Regurgitation
Mitral Insufficiency
Mitral Valve
MR
Mitral Valve Prolapse
E2E - Edge to Edge
Alfieri Technique

MitraClip
Functional MR
Degenerative MR
Echocardiogram
CAD - Coronary Artery Disease
Heart Failure
Heart Attack
EVEREST
EVEREST I
EVEREST II

Additional relevant MeSH terms:

Mitral Valve Insufficiency
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 09, 2012