Reduction of Elimination of Mitral Regurgitation With the SATURN TMVR System (CASSINI-US)

Official title

Reduction or Elimination of Mitral Regurgitation With the SATURN Trans-septal TMVR System in Patients With Severe, Symptomatic Mitral Regurgitation (Cassini-US)

Overview

CASSINI-US is a prospective, single-arm, multicenter early feasibility study enrolling up to 15 patients at up to 5 sites in the United States (US). The purpose of the study is to evaluate the technical (implant) feasibility, and safety, and performance of the SATURN TS TMVR System for the treatment of moderate-severe or severe, symptomatic mitral regurgitation through a transcatheter approach. Primary objectives evaluate the implant feasibility, and acute safety and performance of the SATURN TS TMVR System. The secondary objective and additional outcome measures characterize the long-term safety and performance of the SATURN TS TMVR System.

Detailed description

The SATURN Bioprosthesis is designed to be implanted in the native mitral heart valve without open-heart surgery, extracorporeal circulation, cardiac arrest or removal of the failed native valve. The SATURN Bioprosthesis consists of the annular structure (Annular Segments) and the valve (SATURN Valve).

The valve supports a set of prosthetic leaflets that are the functional elements of the bioprosthesis. The valve is made of a self-expandable Nitinol frame supports three bovine pericardium leaflets. The valve is assembled with the annular structure through two connecting blocks mounted on the connecting arms of the stent.

The SATURN Delivery System and Accessories provides a transcatheter pathway to deliver the SATURN valve through the septum via the femoral vein. The SATURN Delivery System consists of an outer sheath, a guidewire delivery system, a valve delivery system and accessories.

The use of the SATURN TS System is carried out according to precise specifications and indications specified in the Instructions for Use (IFU) and is restricted to those physicians who have undergone dedicated training on use of the device.

Participants will be screened based on predefined inclusion and exclusion criteria. Eligible subjects will provide informed consent prior to any study-related procedures.

The clinical study designed to evaluate the safety, performance, and long-term clinical outcomes in adult patients with cardiac conditions. The study aims to collect comprehensive clinical data across patient population to support the understanding of procedural success, device-related outcomes, and patient recovery over time.

Participants will be followed from screening through five years post-procedure, with scheduled evaluations at the following timepoints: Screening, Baseline (pre-procedure), Intraprocedural, 24-48 hours post-procedure, 7 days or discharge, 1 month (±7 days), 3 months (±14 days), 6 months (±30 days), 1 year (±30 days), and annually through year five (±60 days).

Clinical assessments include physical examination, vital signs, and review of cardiac and antithrombotic medications. Functional status is evaluated using the Modified Rankin Scale, New York Heart Association (NYHA) classification, and the 6-Minute Walk Test. Quality of life is assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Risk stratification is performed at screening using EuroSCORE II and STS Risk Score.

Laboratory testing includes hematology, coagulation profiles, renal and liver function tests , and cardiac biomarkers such as NT-proBNP and plasma-free hemoglobin. Pregnancy testing is conducted at baseline for applicable participants.

Imaging and diagnostic testing includes transthoracic and transesophageal echocardiography (TTE/TEE), cardiac and vascular CT, gated cardiac CT at 6 months, 12-lead ECG, and intraprocedural assessments such as fluoroscopy, angiography, and right heart catheterization.

Safety endpoints include the incidence of adverse events (AEs), device deficiencies or malfunctions, and protocol deviations. The study is designed to generate robust clinical evidence supporting the intervention's safety, efficacy, and durability over time, and to inform future clinical practice and regulatory submissions.

Interventions

• Device Mitral Valve Replacement
  Implant of SATURN TS TMVR System for the treatment of moderate-severe or severe, symptomatic mitral regurgitation

Primary outcome measures

• Technical (Implant) Success Endpoint [Time frame: At completion of study procedure (Day 0)]
• Freedom from Major Adverse Events Endpoint [Time frame: 30 days from index procedure]
• Mitral Valve Effectiveness Endpoint (reduction in MR grade) [Time frame: 30 days post treatment]

Secondary outcome measures (1)

• Mitral Valve Performance over time Endpoint [Time frame: 5 years post index procedure]

Eligibility criteria

Inclusion criteria

• Age 18 years or older.
• Symptomatic, moderate to severe or severe, functional or mixed, mitral regurgitation (≥ Grade 3+).
• NYHA functional Class ≥ II. If Class IV, patient must be ambulatory.
• Ability to tolerate oral anticoagulation.
• Ability to qualify for bailout surgery (which may include open heart surgery).
• High risk for open-heart mitral valve surgery due to age, co-morbidities or frailty, as determined by the Heart Team.
• Willing and able to complete study-related assessments and questionnaires.

Exclusion criteria

• Purely degenerative (organic/primary) (i.e. intrinsic valve lesions) mitral regurgitation.
• Excessive frailty or comorbid conditions that preclude the anticipated benefit of the mitral valve replacement.
• Life expectancy <1 yr. due to noncardiac conditions.
• Endocarditis in the 3 months prior to procedure date.
• Current admission with acute heart failure exacerbation.
• Dependency on inotropic agents or mechanical circulatory support.
• Untreated clinically significant CAD.
• Active systemic infection.
• Modified Rankin Scale ≥4 disability.
• Chronic renal failure defined as eGFR < 30 mL/min/m2 or on renal replacement therapy.
• Severe pulmonary arterial hypertension (PAH), defined as PASP > 70mmHg.
• Platelets < 90,000.
• COPD on home oxygen therapy deemed too high risk for intubation.
• Refuses blood transfusions.
• Documented bleeding or coagulation disorders (hypo- or hyper-coagulable states).
• Severe connective tissue disease under chronic immunosuppressive or cortisone therapy.
• Participating in other investigational studies likely to confound the results or affect the study.
• Unable or does not sign the study informed consent form.
• Patients classified as "vulnerable patients"

Cardiovascular Exclusion Criteria

• Myocardial infarction during prior 30 days.
• Stroke or TIA during prior 90 days.
• Severe extracardiac arteriopathy (safety measure for extra-circulatory support if surgical conversion is needed).
• Prior mitral valve treatment (e.g., valve repair or replacement, MitraClip, etc.), and/or anticipated mitral valve treatment prior to enrollment.
• Prior surgical mechanical valve AVR.
• Prior TAVI. -Need for any planned cardiovascular surgery or intervention (other than for MV disease) within 30 days post-index procedure.
• CRT, CRT-D, IPG or ICD implanted in previous 30 days.
• Cardiogenic shock, hemodynamic instability, Systolic Blood Pressure <90mmHg, Inotropic dependent or IABP/mechanical circulatory support.

CABG or PCI within previous 30 days.

• Inadequately treated for cardiac condition per applicable standards, such as for coronary artery disease, left ventricular dysfunction, mitral regurgitation, or heart failure, as reviewed by the Patient Screening Committee.
• Prior or planned heart transplantation (UNOS status 1).
• Physical evidence of right-sided CHF:

• Patients with ascites.
• Patients with anasarca (generalized edema / hydropsy).
• Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or other structural heart disease causing heart failure with the exception of dilated ischemic or non-ischemic cardiomyopathy.

Procedural Exclusion Criteria

• Known hypersensitivity or contraindication to procedural or post-procedural medication (e.g., contrast solution, anticoagulation therapy).
• Documented hypersensitivity to nickel or titanium.

Cardiac Imaging Exclusion Criteria (evaluated by Core Labs)

• Contraindications to TEE imaging
• Left ventricular EF ≤ 30% by echocardiogram.
• Severe mitral annular calcification, severe mitral stenosis, valvular vegetation or mass.
• Extensive mitral flail leaflets
• Evidence of new or untreated intracardiac thrombus, mass, or vegetation.
• Severe right ventricular dysfunction.
• Severe tricuspid regurgitation.
• Hemodynamically significant inter-atrial shunt (ASD).
• Severe aortic regurgitation or aortic stenosis.
• Anatomic ineligibility for SATURN Valve or SATURN TS procedure as determined by the Screening Committee.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Cedars-Sinai Medical Center — Los Angeles
• UC Davis Health — Sacramento
• Los Robles Regional Medical Center — Thousand Oaks
• Columbia University Irving Medical Center/New York Presbyterian Hospital — New York
• Oregon Health & Science University — Portland

Identifiers

NCT: NCT07130994 · TP-0144

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗