Clinical trial NCT02444338: A Clinical Evaluation of the Safety and Effectiveness of the MitraClip System in the Treatment of Clinically Significant Functional Mitral Regurgitation
Official title: Randomised Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients With Clinically Significant Functional Mitral Regurgitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mitral Valve Insufficiency
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
First posted: 2015-05-14
Enrollment: 505
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To study the safety and effectiveness of the MitraClip System in the treatment of clinically significant functional mitral regurgitation in patients with New York Heart Association (NYHA) Functional Class II to Class IV chronic heart failure.

Detailed description: The trial is designed to provide additional evidence regarding appropriate recommendations for use of the MitraClip System for patients with chronic heart failure and clinically significant functional mitral regurgitation. Additionally, the trial will collect evidence regarding health economics of the MitraClip System for use in this patient population.

Eligibility criteria: Key Inclusion Criteria:

* Clinically significant functional mitral regurgitation (moderate-to-severe or severe MR) as defined by European Association of Echocardiography, within 90 days prior to randomization and confirmed by the Echocardiography Core Laboratory Note: The TTE must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
* Assessed by the investigator to be on optimal standard of care therapy for heart failure, according to current ESC/HFA guidelines with no dose changes of heart failure drugs (with the exception of diuretics) during the last 2 weeks immediately prior to randomization.
* Symptomatic with documented New York Heart Association Class II, III or IV heart failure, despite optimal standard of care therapy, within 30 days preceding randomization
* Minimum of one documented hospitalization (acute care admission or emergency room visit) for heart failure within 12 months preceding randomization OR values of 300 pg/mL for BNP or 1000 pg/mL for NT-proBNP after optimal medical and/or device management within 90 days preceding randomization Note: BNP or NT-proBNP must be obtained after the subject has been stabilized on optimal therapy and has undergone revascularization and/or CRT, as appropriate
* Ambulatory patient with symptomatic congestive heart failure (CHF) in NYHA functional class II to IV (despite optimal standard of care therapy as assessed within 30 days preceding randomization) and with LVEF 20% to 50%. Note: LVEF needs to be determined by one of the following methods: transthoracic echocardiography (TTE), contrast ventriculography, gated blood pool scan, cardiac magnetic resonance) within 90 days prior to randomization
* Patient is ambulatory and able to perform a 6MWT with the only limiting factor(s) being due to cardiovascular fitness

Key Exclusion Criteria:

* Mitral regurgitation is primarily due to degenerative disease of the mitral valve apparatus (Degenerative MR) as determined by transesophageal echocardiography (TEE).
* Status 1 heart transplant or prior orthotropic heart transplantation.
* Introduction of a new heart failure drug class within the last 2 weeks prior to randomization.
* Evidence of acute coronary syndrome, transient ischemic attack or stroke within 90 days prior to randomization. Note:Acute coronary syndrome (ACS) is defined as an ACS that requires an intervention. Increased troponin without acute symptoms and chest pain is not defined as ACS.
* Any percutaneous cardiovascular intervention, carotid surgery, cardiovascular surgery, or atrial fibrillation ablation within 90 days prior to randomization.
* Therapy with or without cardioverter-defibrillator (CRT or CRT-D), or Implantable Cardioverter Defibrillator (ICD)) within 90 day prior to randomization, or revision of any implanted rhythm management device within 90 days prior to randomization.
* Need for any cardiovascular surgery.
* Mitral valve surgery is considered the preferred therapeutic option for the subject
* Renal replacement therapy
* 6-Minute Walk Test (6MWT) distance \> 475 meters
* Mitral Valve Area (MVA) by planimetry \< 4.0 cm2; if MVA by planimetry is not measurable, pressure half-time measurement is acceptable; MVA must be confirmed by the Echocardiography Core Laboratory

Primary outcomes:
measure: Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death within 24 months
timeFrame: 24 months
measure: Rate of total (first and recurrent) HF hospitalizations within 24 months
timeFrame: 24 months
measure: Change in quality of life (i.e. overall KCCQ score) from baseline to 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Percentage of patients with mitral regurgitation grade of 2+ or lower at 12 months as assessed by the Echocardiography Core Laboratory
timeFrame: at 12 months
measure: Change in 6 Minute Walking Test distance from baseline to 12 months
timeFrame: from baseline to 12 months
measure: All-cause mortality during all available follow-up
timeFrame: during all available follow-up
measure: Rate of total (first and recurrent) hospitalizations for any cause within 24 months
timeFrame: 24 months
measure: Percentage of patients in NYHA function class I/II at 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Klinika Kardiologie IKEM
city: Copenhagen
country: Denmark
facility: Rigshospitalet Copenhagen
city: Odense
country: Denmark
facility: OUH Odense
city: Berlin
country: Germany
facility: Charité
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Genthin
country: Germany
facility: Johanniter Krankenhaus
city: Göttingen
country: Germany
facility: University Medical Center Goettingen
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Mainz
country: Germany
facility: University Hospital Mainz
city: Würzburg
country: Germany
facility: Universitätsklinik Würzburg
city: Athens
country: Greece
facility: HYGEIA Hospital Athens
city: Thessaloníki
country: Greece
facility: Interbalkan Medical Center
city: Thessaloníki
country: Greece
facility: St. Luke's Hospital Thessaloniki
city: Brescia
country: Italy
facility: AOC Brescia
city: Katowice
country: Poland
facility: Cardiology Department at Samodzielny Publiczny Szpital Kliniczny nr 7
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im. Jana Pawła II
city: Poznań
country: Poland
facility: Poznan Medical University
city: Wrocław
country: Poland
facility: Medical University Department of Heart Diseases
city: Zabrze
country: Poland
facility: Śląskie Centrum Chorób Serca
city: Lisbon
country: Portugal
facility: Lisbon St. Marta Hospital
city: Lisbon
country: Portugal
facility: Lisbon St. Maria Hospital
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia / Espinho
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Leon
country: Spain
facility: HUL Leon
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Valladolid
country: Spain
facility: Instituto de Ciencias del Corazón (ICICOR)
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Glasgow
country: United Kingdom
facility: Golden Jubilee National Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: London
country: United Kingdom
facility: The Royal Brompton and Harefield Hospitals
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital of South Manchester - Manchester University NHS Foundation Trust (MFT)
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke Hospital - University Hospital of North Midlands
Study officials:
affiliation: University Medical Center Göttingen
name: Wolfgang Schillinger, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anker SD, Friede T, von Bardeleben RS, Butler J, Khan MS, Diek M, Heinrich J, Geyer M, Placzek M, Ferrari R, Abraham WT, Alfieri O, Auricchio A, Bayes-Genis A, Cleland JGF, Filippatos G, Gustafsson F, Haverkamp W, Kelm M, Kuck KH, Landmesser U, Maggioni AP, Metra M, Ninios V, Petrie MC, Rassaf T, Ruschitzka F, Schafer U, Schulze PC, Spargias K, Vahanian A, Zamorano JL, Zeiher A, Karakas M, Koehler F, Lainscak M, Oner A, Mezilis N, Theofilogiannakos EK, Ninios I, Chrissoheris M, Kourkoveli P, Papadopoulos K, Smolka G, Wojakowski W, Reczuch K, Pinto FJ, Wiewiorka L, Kalarus Z, Adamo M, Santiago-Vacas E, Ruf TF, Gross M, Tongers J, Hasenfuss G, Schillinger W, Ponikowski P; RESHAPE-HF2 Investigators. Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation. N Engl J Med. 2024 Nov 14;391(19):1799-1809. doi: 10.1056/NEJMoa2314328. Epub 2024 Aug 31.
citation: Anker SD, Friede T, von Bardeleben RS, Butler J, Fatima K, Diek M, Heinrich J, Hasenfuss G, Schillinger W, Ponikowski P. Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design. Eur J Heart Fail. 2024 Apr;26(4):984-993. doi: 10.1002/ejhf.3247. Epub 2024 Apr 23.