A Clinical Evaluation of the Safety and Effectiveness of the MitraClip System in the Treatment of Clinically Significant Functional Mitral Regurgitation (Reshape-HF2)

Randomised Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients With Clinically Significant Functional Mitral Regurgitation

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.

Study Overview

• Status: Completed
• Conditions: Mitral Valve Insufficiency
• Intervention / Treatment: Other: standard of care; Device: MitraClip

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.

• Study Type: Interventional
• Enrollment (Actual): 505
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 14021
    • Klinika Kardiologie IKEM
• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet Copenhagen
  • Odense, Denmark
    • OUH Odense
• Germany
  • Berlin, Germany, 12200
    • Charité
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Genthin, Germany, 39576
    • Johanniter Krankenhaus
  • Göttingen, Germany, 37075
    • University Medical Center Goettingen
  • Halle, Germany, 06097
    • Universitatsklinikum Halle
  • Heidelberg, Germany, 69120
    • University Hospital Heidelberg
  • Jena, Germany, 07747
    • Universitatsklinikum Jena
  • Mainz, Germany, 55131
    • University Hospital Mainz
  • Würzburg, Germany, 97080
    • Universitätsklinik Würzburg
• Greece
  • Athens, Greece
    • HYGEIA Hospital Athens
  • Thessaloníki, Greece, 57001
    • Interbalkan Medical Center
  • Thessaloníki, Greece
    • St. Luke's Hospital Thessaloniki
• Italy
  • Brescia, Italy
    • AOC Brescia
• Poland
  • Katowice, Poland, 40-635
    • Cardiology Department at Samodzielny Publiczny Szpital Kliniczny nr 7
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im. Jana Pawła II
  • Poznań, Poland, 61-848
    • Poznan Medical University
  • Wrocław, Poland, 50981
    • Medical University Department of Heart Diseases
  • Zabrze, Poland, 41-800
    • Slaskie Centrum Chorob Serca
• Portugal
  • Lisbon, Portugal, 1169-1024
    • Lisbon St. Marta Hospital
  • Lisbon, Portugal
    • Lisbon St. Maria Hospital
  • Vila Nova de Gaia, Portugal
    • Centro Hospitalar Vila Nova de Gaia / Espinho
• Spain
  • Badalona, Spain
    • Hospital Germans Trias i Pujol
  • Leon, Spain
    • HUL Leon
  • Oviedo, Spain
    • Hospital Universitario Central de Asturias
  • Valladolid, Spain
    • Instituto de Ciencias del Corazón (ICICOR)
• United Kingdom
  • Edinburgh, United Kingdom
    • Royal Infirmary of Edinburgh
  • Glasgow, United Kingdom
    • Golden Jubilee National Hospital
  • Hull, United Kingdom
    • Castle Hill Hospital
  • London, United Kingdom
    • The Royal Brompton and Harefield Hospitals
  • Manchester, United Kingdom
    • Wythenshawe Hospital of South Manchester - Manchester University NHS Foundation Trust (MFT)
  • Stoke-on-Trent, United Kingdom
    • Royal Stoke Hospital - University Hospital of North Midlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; optimal standard of care therapy	Other: standard of care
Experimental: Device Group; MitraClip device plus optimal standard of care therapy	Other: standard of care; Device: MitraClip; Implantation of the MitraClip System for patients with chronic heart failure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death within 24 months	Composite rate of recurrent heart failure hospitalizations and cardiovascular (CV) death within 24 months	24 months
Rate of total (first and recurrent) HF hospitalizations within 24 months	Rate of total (first and recurrent) HF hospitalizations within 24 months	24 months
Change in quality of life (i.e. overall KCCQ score) from baseline to 12 months	Change in quality of life (i.e. overall KCCQ score) from baseline to 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with mitral regurgitation grade of 2+ or lower at 12 months as assessed by the Echocardiography Core Laboratory	Percentage of patients with mitral regurgitation grade of 2+ or lower at 12 months as assessed by the Echocardiography Core Laboratory	at 12 months
Change in 6 Minute Walking Test distance from baseline to 12 months	Change in 6 Minute Walking Test distance from baseline to 12 months	from baseline to 12 months
All-cause mortality during all available follow-up	All-cause mortality during all available follow-up	during all available follow-up
Rate of total (first and recurrent) hospitalizations for any cause within 24 months	Rate of total (first and recurrent) hospitalizations for any cause within 24 months	24 months
Percentage of patients in NYHA function class I/II at 12 months	Percentage of patients in NYHA function class I/II at 12 months	12 months

Collaborators and Investigators

• Sponsor: University Medical Center Goettingen
• Collaborators: University Medical Center Goettingen
• Investigators: Principal Investigator: Wolfgang Schillinger, Prof., University Medical Center Göttingen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): April 19, 2024
• Study Completion (Actual): April 19, 2024

Study Registration Dates

• First Submitted: May 12, 2015
• First Submitted That Met QC Criteria: May 13, 2015
• First Posted (Estimated): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Mitral Valve Insufficiency
• Other Study ID Numbers: Version No. 6.0