Noninferiority Trial of MitraClip Implantation Strategies: 1 Clip vs. 2 Clips in Patients With Functional Mitral Regurgitation (One-Plus-One)

Noninferiority Trial of MitraClip Implantation Strategies: 1 Clip vs. 2 Clips in Patients With Functional Mitral Regurgitation (One-Plus-One)

Implantation of the MitraClip has become the most frequently used percutaneous technique to treat significant (grade 3+ or 4+) mitral regurgitation (MR) in elderly patients deemed inoperable or at high surgical risk. In Europe, about two-thirds of patients treated with the MitraClip suffer from MR of functional origin secondary to ischemic or dilated cardiomyopathy. At present, there is debate among operators on whether stabilizing/supporting a single adequately implanted clip with a second clip is beneficial for patients with functional MR.

Study Overview

• Status: Withdrawn
• Conditions: Mitral Regurgitation Functional
• Intervention / Treatment: Device: MitraClip implantation

Detailed Description

Implantation of the MitraClip has become the most frequently used percutaneous technique to treat significant (grade 3+ or 4+) mitral regurgitation (MR) in elderly patients deemed inoperable or at high surgical risk. In Europe, about two-thirds of patients treated with the MitraClip suffer from MR of functional origin secondary to ischemic or dilated cardiomyopathy. At present, there is debate among operators on whether stabilizing/supporting a single adequately implanted clip with a second clip is beneficial for patients with functional MR.

Purpose To demonstrate the noninferiority of a 1-clip strategy vs. a 2-clip strategy of MitraClip implantation, when the second clip in the 2-clip study arm is implanted for stabilizing/supporting purposes.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Absence of a structural abnormality of the mitral valve giving rise to MR.
• MR severity of US grade 3+ or 4+ of central or noncentral origin
• Patient must consent to randomization in the hybrid operating theater upon successful implantation of a single MitraClip. Written informed consent must be provided prior to the MitraClip procedure.

Exclusion Criteria:

• patients with primary regurgitation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: One CLIP; Implantation of single MitraClip	Device: MitraClip implantation; Device to approximate the mitral valve leaflets
Active Comparator: Two CLIPs; Implantation of second MitraClip (after successful Implantation of single MitraClip)	Device: MitraClip implantation; Device to approximate the mitral valve leaflets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of number of participants who died death within one year	death	1 year
Evaluation of number of rehospitalizations due to heart failure among patients receiving one or two clips	heart failure rehospitalization	1 year
Evaluation of number of participants with recurrent regurgitation within one year	recurrence of mitral regurgitation (>grade 2+ at 1 year)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death	freedom from death (1-year)	1 year
heart failure	freedom from heart failure (1-year)	1 year
rehospitalization	rehospitalization	1-year
regurgitation	freedom from recurrence of mitral regurgitation (>2+; 1-year)	1-year
success rate	procedural success rate in 2-clip arm	1-year
procedure duration	procedure duration	1-year
total device time	total device time	1-year
fluoroscopy time	fluoroscopy time	1-year
contrast volume	contrast volume	1-year
complications	periprocedural (30-day) complications	1-year
echocardiographic variables	The following echocardiographic variables will be assessed by 2-dimensional transthoracic echocardiography at 12 months: Left ventricular (LV) end-diastolic diameter and volume; LV end-systolic diameter and volume; LV ejection fraction; LV outflow tract diameter and velocity time integral in LV outflow tract (to calculate forward stroke volume).	1-year
changes in echocardiographic variables	Changes from baseline to 12 months in echocardiographically assessed (at both time points) LV end-diastolic diameter and volume; LV end-systolic diameter and volume; LV ejection fraction; and forward stroke volume.	1-year
NYHA	NYHA functional class	1-year
6-minutes walk	6-minutes walk distance	1-year
quality of life	Assessment of the Minnesota Living With Heart Failure Questionnaire (MLHFQ) quality-of-life score. The questionnaire consists of 21 quality-of-life questions to be answered by the patient on a grading scale of 0 (best) to 5 (worst). Thus, the overall MLHFQ score ranges from 0 to 105.	1-year

Collaborators and Investigators

• Sponsor: Asklepios proresearch
• Collaborators: Abbott
• Investigators: Principal Investigator: Karl-Heinz Kuck, MD, PHD, Asklepios Klinik St. Georg, Dept. of Cardiology

Publications and helpful links

General Publications

• Franzen O, Baldus S, Rudolph V, Meyer S, Knap M, Koschyk D, Treede H, Barmeyer A, Schofer J, Costard-Jackle A, Schluter 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. doi: 10.1093/eurheartj/ehq050. Epub 2010 Mar 10.
• Feldman T, Foster E, Glower DD, 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. doi: 10.1056/NEJMoa1009355. Epub 2011 Apr 4. Erratum In: N Engl J Med. 2011 Jul 14;365(2):189. Glower, Donald G [corrected to Glower, Donald D].
• Maisano F, Franzen O, Baldus S, Schafer U, Hausleiter J, Butter C, Ussia GP, Sievert H, Richardt G, Widder JD, Moccetti T, Schillinger W. Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol. 2013 Sep 17;62(12):1052-1061. doi: 10.1016/j.jacc.2013.02.094. Epub 2013 Jun 7.
• Baldus S, Schillinger W, Franzen O, Bekeredjian R, Sievert H, Schofer J, Kuck KH, Konorza T, Mollmann H, Hehrlein C, Ouarrak T, Senges J, Meinertz T; German Transcatheter Mitral Valve Interventions (TRAMI) investigators. MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry. Eur J Heart Fail. 2012 Sep;14(9):1050-5. doi: 10.1093/eurjhf/hfs079. Epub 2012 Jun 8.
• Feldman T, Kar S, Elmariah S, Smart SC, Trento A, Siegel RJ, Apruzzese P, Fail P, Rinaldi MJ, Smalling RW, Hermiller JB, Heimansohn D, Gray WA, Grayburn PA, Mack MJ, Lim DS, Ailawadi G, Herrmann HC, Acker MA, Silvestry FE, Foster E, Wang A, Glower DD, Mauri L; EVEREST II Investigators. Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation: 5-Year Results of EVEREST II. J Am Coll Cardiol. 2015 Dec 29;66(25):2844-2854. doi: 10.1016/j.jacc.2015.10.018.
• Grasso C, Capodanno D, Scandura S, Cannata S, Imme S, Mangiafico S, Pistritto A, Ministeri M, Barbanti M, Caggegi A, Chiaranda M, Dipasqua F, Giaquinta S, Occhipinti M, Ussia G, Tamburino C. One- and twelve-month safety and efficacy outcomes of patients undergoing edge-to-edge percutaneous mitral valve repair (from the GRASP Registry). Am J Cardiol. 2013 May 15;111(10):1482-7. doi: 10.1016/j.amjcard.2013.01.300. Epub 2013 Feb 20.
• Surder D, Pedrazzini G, Gaemperli O, Biaggi P, Felix C, Rufibach K, der Maur CA, Jeger R, Buser P, Kaufmann BA, Moccetti M, Hurlimann D, Buhler I, Bettex D, Scherman J, Pasotti E, Faletra FF, Zuber M, Moccetti T, Luscher TF, Erne P, Grunenfelder J, Corti R. Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry. Heart. 2013 Jul;99(14):1034-40. doi: 10.1136/heartjnl-2012-303105. Epub 2013 Jan 23.
• Nickenig G, Estevez-Loureiro R, Franzen O, Tamburino C, Vanderheyden M, Luscher TF, Moat N, Price S, Dall'Ara G, Winter R, Corti R, Grasso C, Snow TM, Jeger R, Blankenberg S, Settergren M, Tiroch K, Balzer J, Petronio AS, Buttner HJ, Ettori F, Sievert H, Fiorino MG, Claeys M, Ussia GP, Baumgartner H, Scandura S, Alamgir F, Keshavarzi F, Colombo A, Maisano F, Ebelt H, Aruta P, Lubos E, Plicht B, Schueler R, Pighi M, Di Mario C; Transcatheter Valve Treatment Sentinel Registry Investigators of the EURObservational Research Programme of the European Society of Cardiology. Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry. J Am Coll Cardiol. 2014 Sep 2;64(9):875-84. doi: 10.1016/j.jacc.2014.06.1166.
• Eggebrecht H, Schelle S, Puls M, Plicht B, von Bardeleben RS, Butter C, May AE, Lubos E, Boekstegers P, Ouarrak T, Senges J, Schmermund A. Risk and outcomes of complications during and after MitraClip implantation: Experience in 828 patients from the German TRAnscatheter mitral valve interventions (TRAMI) registry. Catheter Cardiovasc Interv. 2015 Oct;86(4):728-35. doi: 10.1002/ccd.25838. Epub 2015 Feb 12.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2018
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: April 11, 2018
• First Posted (Actual): April 20, 2018

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: January 2, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Mitral Regurgitation; MitraClip; transcatheter mitral valve repair
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: #3150

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No