GISE Registry of Transcatheter Treatment of Mitral Valve Regurgitation With the MitraClip G4

The GIOTTO4 Study: GISE Registry of Transcatheter Treatment of Mitral Valve Regurgitation With the MitraClip G4

The aim of the GISE study is to confirm the MitraClip safety and improve the device effectiveness in a selected all comers ("more-comers") population with symptomatic severe mitral regurgitation undergoing/undergone Transcatheter Edge-to-Edge Repair (TEER) with MitraClip G4.

Study Overview

• Status: Recruiting
• Conditions: Mitral Valve Regurgitation

• Study Type: Observational
• Enrollment (Estimated): 264

Contacts and Locations

Study Locations

• Italy
  • Milano
    • San Donato Milanese, Milano, Italy, 20097
      • Recruiting
      • I.R.C.C.S. Policlinico San Donato
      • Contact: Federica Rossi; Phone Number: +390252774987; Email: Federica.Rossi@grupposandonato.it
      • Principal Investigator: Antonio Popolo Rubbio, MD
      • Sub-Investigator: Francesco Bedogni, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing/undergone to TEER procedure with MitraClip G4 in selected hospitals linked to the GISE network. Patients should meet all the inclusion criteria and none of the exclusion criteria; such criteria will identify a selected all comers ("more-comers") population which includes the vast majority of patients treated with MitraClip in daily practice. Retrospective enrolments are allowed if available data are in line with the study requirements and the patients can give their consent to be enrolled in the study informed consent process. Patients who don't meet one or more of the inclusion criteria or met at least one exclusion criteria are excluded from the study; however, a selected list of baseline/procedural features and follow-up data will be recorded for excluded patients.

Description

Inclusion Criteria:

SUBGROUP A: FUNCTIONAL MR Patients with symptomatic severe secondary MR (3-4+, according to the multiparametric study algorithm), both ischemic or non-ischemic etiology, on optimal medical therapy AND

• Left Ventricular End-Systolic Dimension <70 mm
• Mitral Valve area > 4 cmq
• Left ventricular ejection fraction ≥20%
• NYHA functional class II, III, ambulatory IV
• brain natriuretic peptide BNP ≥300 pg/ml or N-terminal prohormone of brain natriuretic peptide NT-proBNP ≥1500 pg/ml and/or at least one hosp for HF (Heart failure) in the 12 months prior to enrollment
• Age 18 years or older
• Subject has been adequately treated per applicable standards, including for coronary artery disease, LV (left ventricular) dysfunction, MR Mitral (regurgitation) and HF
• Local Heart-team decision SUBGROUP B: DEGENERATIVE MR Patients with symptomatic severe primary MR (3-4+, according to the multiparametric study algorithm) AND
• Mobile mitral valve (MV) length of PL ≥8 mm in case of NT device, ≥10 mm in case of XT device
• MV area > 4 cm2
• NYHA functional class > II
• Age 18 years or older
• Local HT decision In case of patients with a coexistence of both etiologies, they will be assigned to a subgroup based on the prevailing mechanism.

THE MULTIPARAMETRIC ALGORITHM FOR MR GRADING The multiparametric algorithm, adapted from the criteria recommended by the American Society of Echocardiography 2003 Guidelines and based on 3 tiers of evaluation, will be used for qualification purposes to determine if MR was 3+ or higher. The 3 tiers of evaluation are applied in a hierarchical manner (from tier 1 to 3) and patients qualified for TEER by meeting the criteria of at least one of them. For MR grading purposes, MR severity was subsequently graded as 3+ or 4+ based on the integrative evaluation of multiple parameters recommended by the The American Society of Echocardiography (ASE)

Exclusion Criteria:

• Significant right ventricular disfunction (TAPSE<15 mm and/or S'<8cm/s)
• Systolic pulmonary artery > 70 mmHg with irreversible precapillary pulmonary hypertension
• Severe TR Tricuspid valve regurgitation
• Hemodynamic instability/NYHA IV
• Impaired mobility as a result of neurological or musculoskeletal disease, or advanced dementia
• Leaflet anatomy which may preclude MitraClip implantation, proper MitraClip positioning on the leaflets or sufficient reduction in MR by the MitraClip
• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, infiltrative cardiomyopathies
• CABG coronary artery bypass graft, PCI percutaneous coronary intervention, TAVR transcatheter aortic valve replacement, CVA cardiovascular accident within the prior 60 days
• Life expectancy <12 months due to non-cardiac conditions
• Active infections
• Advanced HF (ESC/HFA Heart Failure Association Criteria) or Bridge tp to HTx/LVAD (left ventricular assist device)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
FUNCTIONAL MR; Patients with symptomatic severe secondary MR (3-4+, according to the multiparametric study algorithm), both ischemic or non-ischemic etiology, on optimal medical therapy
DEGENERATIVE MR; Patients with symptomatic severe primary MR (3-4+, according to the multiparametric study algorithm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of participants with a mitral regurgitation (MR)	grade ≤1+. Two separates subgroups will be identified according to the presence of functional (FMR) or degenerative (DMR) mitral valve disease.	at 30 days
percentage of participants with a mitral regurgitation (MR)	grade ≤1+. Two separates subgroups will be identified according to the presence of functional (FMR) or degenerative (DMR) mitral valve disease.	at 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite of all-cause death and hospitalization for heart failure (HF),	all-cause death, cardiovascular death and non-cardiovascular death, myocardial infarction, hospitalizations for HF,	at 30 days
composite of all-cause death and hospitalization for heart failure (HF),	all-cause death, cardiovascular death and non-cardiovascular death, myocardial infarction, hospitalizations for HF,	at 1 year
composite of all-cause death and hospitalization for heart failure (HF),	all-cause death, cardiovascular death and non-cardiovascular death, myocardial infarction, hospitalizations for HF,	at 2 years
composite of all-cause death and hospitalization for heart failure (HF),	all-cause death, cardiovascular death and non-cardiovascular death, myocardial infarction, hospitalizations for HF,	at 3 years
composite of all-cause death and hospitalization for heart failure (HF),	all-cause death, cardiovascular death and non-cardiovascular death, myocardial infarction, hospitalizations for HF,	at 4 years
composite of all-cause death and hospitalization for heart failure (HF),	all-cause death, cardiovascular death and non-cardiovascular death, myocardial infarction, hospitalizations for HF,	at 5 years

Collaborators and Investigators

• Sponsor: Fondazione GISE Onlus
• Collaborators: University of Padova; Abbott

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2023
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: July 8, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Estimated): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 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: GISE_GIOTTO4

Drug and device information, study documents

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