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High and Intermediate Risk Degenerative Mitral Regurgitation Treatment: A Trial Comparing MitraClip® to Surgical Therapy

Phase 4
Terminated
Conditions
Mitral Valve Insufficiency
Interventions
Device: MitraClip®
Procedure: Mitral valve Surgery
Registration Number
NCT02534155
Lead Sponsor
University of Zurich
Brief Summary

The study is comparing MitraClip® to Surgical therapy in high and intermediate risk patients, who should be older than 18 years, and shall evaluate safety and efficacy of MitraClip® vs. surgery in high or intermediate risk patients. The patients will be randomised (MitraClip® or Surgery). The Study Follow-Up includes 4 visits after procedure (hospital discharge, 1, 6, 12 months post-procedure).

Detailed Description

Two-arm, multi-centre, randomised prospective study comparing MitraClip® to Surgical therapy in high and intermediate risk patients. Patients should be older than 18 years and high and intermediate risk is defined by a score (for MV repair) \>= 3% and \<= 10% or as determined by the local Heart Team (which should include a surgeon and a cardiologist), based on the evidence that STS risk calculator may not identify all possible risk factors. Patients are selected upon clinical conditions and severity of MR. Anatomical feasibility is assessed by ECHO, according to the IFU (information for use).

The purpose of the trial is to evaluate safety and efficacy of MitraClip® vs. surgery in high and intermediate risk patients with DMR. Study Follow-Up includes the following visits after procedure: Hospital discharge, 1, 6, 12 months post-procedure.

Primary Endpoints are the 30-day safety superiority (ITT analysis) and the 12-month efficacy non-inferiority (ITT analysis) of the MitraClip®. The overall rate of Serious Adverse Events (SAEs) and Serious Adverse Device Events (SADEs) until 12 months and the MR Severity reduction at 6 and 12 month in the MitraClip® and Surgery groups are Secondary Endpoints

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
294
Inclusion Criteria
  • Gender: Both, male and female
  • Minimum Age: 18 Years
  • Maximum Age: no maximum age
  • Severe (4+) DMR (degenerative mitral regurgitation), or 3+ DMR
  • NYHA Functional Class III or IV
  • Mitral valve anatomy should be suitable for both MitraClip® and Mitral valve surgery (repair or replacement)
  • Subjects meet the following conditions:

Age >18 and high or intermediate risk patients with an STS calculated mortality (using the repair calculator) >=3% and <=10% or as determined by the local Heart Team (which should include a surgeon and a cardiologist), based on the evidence that STS risk calculator may not identify all possible risk factors

  • patient is operable
  • Signed by the subject and dated approved informed consent prior to any study related procedure
  • Available and able to return to study site for post-procedural follow-up examination
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Exclusion Criteria
  • Patient incapable to approve the informed consent or Emergency Cases
  • functional mitral valve pathology
  • evolving endocarditis or active endocarditis in the last 3 months
  • heavily calcified leaflets
  • subjects in whom transesophageal echocardiography is contraindicated
  • subjects in whom transseptal catheterisation is contraindicated
  • presence of any known life threatening (non-cardiac major or progressive disease), non-cardiac disease that will limit the subject's life expectancy to less than one year
  • currently participating in the study of an investigational drug or device
  • untreated clinically significant CAD requiring revascularisation
  • any percutaneous coronary, carotid, endovascular intervention or carotid surgery within 30 days or any coronary or endovascular surgery within 3 months
  • prior mitral valve leaflet surgery or any currently implanted prosthetic mitral valve, or any prior transcatheter mitral valve procedure
  • concomitant and significant aortic or tricuspid valve pathology
  • CVA or TIA within 6 months or severe carotid stenosis (>70% assessed by Ultrasound)
  • contraindication or known allergy to device's components, aspirin, anti-coagulation therapy or contrast media that cannot be adequately managed with premedication
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MitraClip® TherapyMitraClip®MitraClip® system is a CE marked medical device, which consists of two parts (Clip Delivery System and Steerable Guide Catheter). It is a single sized, percutaneously implanted mechanical Clip. The MitraClip® device grasps and coapts the mitral valve leaflets resulting in fixed approximation of the mitral leaflets throughout the cardiac cycle. The procedure is performed in the cardiac catheterisation laboratory with echocardiographic and fluoroscopic guidance while the patient is under general anaesthesia.
SurgeryMitral valve SurgerySurgical therapy of degenerative mitral regurgitation: repair or replacement of mitral valve, clinical standard
Primary Outcome Measures
NameTimeMethod
30-day safety superiority (ITT analysis): Major Adverse Event Composite30 days

The study is powered to show superiority for safety of an endovascular treatment strategy with the MitraClip® as compared to a surgical treatment strategy. The primary safety endpoint is a Major Adverse Event Composite (MAE) including all-cause death, prolonged ventilation (\>48h), renal failure, stroke and need for non-elective cardiovascular or thoracic surgery (defined as any kind of cardiovascular and thoracic surgery performed within 30 days from the index procedure and non anticipated prior to the procedure). The analysis of the primary safety endpoint is a test of superiority for the proportion of subjects free from the composite of safety events in the Device vs. the Surgery group at 30 days.

12-month efficacy non-inferiority (ITT analysis): Proportion of responders in the Device vs. the Surgery group12 month

The study is powered to show non-inferiority for clinical efficacy of an endovascular treatment strategy with the MitraClip® as compared to a surgical treatment strategy. The primary effectiveness endpoint is a test of non-inferiority for the proportion of responders in the Device vs. the Surgery group at 12 months. Patients are defined as responders if they are alive with at least a 1-grade improvement in NYHA Functional Class at 12 months over baseline and have not experienced a HF hospitalization within 12 months of randomization (MitraClip® procedure or Surgery).

Secondary Outcome Measures
NameTimeMethod
Overall rate of Serious Adverse Events (SAEs) and Serious Adverse Device Effects (SADEs) within 12 month12 month

Evaluation of all SAEs and SADEs that occur during the trial

MR Severity reduction at 6 and 12 monthbetween 6 and 12 month

MR (Mitral Regurgitation) Severity reduction at 6 and 12 months in the MitraClip® and Surgery groups

Change in 6MWT in 6 and 12 monthbetween 6 and 12 months

Change in 6MWT (6 Minute Walking Test) in 6 and 12 months in the MitraClip® and Surgery groups

NYHA class changes at 6 and 12 monthsbetween 6 and 12 month

NYHA class changes at 6 and 12 months in the MitraClip® and Surgery groups

Heart failure hospitalisation rateduring 12 months post procedure

Heart failure hospitalisation rate in the post randomisation in the MitraClip® and Surgery groups

Hospital resources utilisationsduring 12 months post procedure

Hospital resources utillizations: length of stay post-procedure, ICU beds occupancy, need for rehabilitation services

Change in Quality of Life in 6 and 12 monthsbetween 1 and 12 months

Change in Quality of Life (MLWHF) at 1,6 and 12 month in the MitraClip® and Surgery groups

Change in Quality of Life (SF36) in 6 and 12 monthsbetween 1 and 12 months

Change in SF36 at 1,6 and 12 month in the MitraClip® and Surgery groups

Days alive and out of hospitalduring 12 months post procedure

Days alive and out of hospital in the 12 months post-randomisation in the MitraClip® and Surgery groups

Trial Locations

Locations (12)

San Raffaele Hospital

🇮🇹

Milano, Italy

Asklepios Klinik Hamburg St. Georg

🇩🇪

Hamburg, Germany

Inselspital Bern

🇨🇭

Bern, Switzerland

Policlinico Tor Vergata

🇮🇹

Roma, Italy

Presidio Ospedaliero Ferrarotto Alessi

🇮🇹

Catania, Italy

Fondazione Cardiocentro Ticino

🇨🇭

Lugano, Switzerland

Universitätsklinikum Bonn

🇩🇪

Bonn, Germany

Universitätsspital Zürich

🇨🇭

Zürich, Switzerland

Universitätsklinikum Köln, Herzzentrum

🇩🇪

Köln, Germany

Klinikum der Universität München Großhadern

🇩🇪

München, Germany

Universitäres Herzzentrum Hamburg GmbH

🇩🇪

Hamburg, Germany

Helios Klinikum Siegburg

🇩🇪

Siegburg, Germany

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