A Clinical Study of X-Clip Mitral Valve Clip System and Steerable Guide System for Transcatheter Mitral Valve Repair of Degenerative Mitral Regurgitation

N/ANot Yet RecruitingNCT07660185

Shenzhen Lifevalve Medical Scientific Co., Ltd.15 enrolled

Overview

Shenzhen Lifevalve Medical Scientific Co., Ltd. has developed a new X-Clip Mitral Valve Clip System and its compatible Steerable Guide System, aiming to provide transcatheter mitral valve repair for patients with degenerative mitral regurgitation. The two systems have completed all preclinical tests, including design verification tests, biological evaluation, and animal studies. All the test results confirmed that the systems met relevant design requirements. A First-in-Man clinical study was conducted in China in 2023, involving 11 patients. The study provides initial evidence that the X-Clip Mitral Valve Clip System and Steerable Guide System demonstrate favourable safety and efficacy in the treatment of mitral regurgitation in the Chinese population. The device is currently undergoing a pivotal clinical trial in China. This study is a clinical study aimed to evaluate the safety and performance of the X-Clip Mitral Valve Clip System and Steerable Guide System in European population.

Mitral regurgitation (MR) is the most prevalent valvular heart disease globally. It is characterized by the backward flow of blood from the left ventricle (LV) into the left atrium (LA) through the mitral valve during systole, usually due to improper closure of the valve leaflets. This hemodynamic impairment can ultimately result in symptoms of heart failure, including fatigue, dyspnea, and progressive left ventricular dysfunction. MR affects 2-3% of the general population, with a prevalence increasing with age. Nearly 1 in 10 individuals aged ≥ 75 years reportedly has moderate or severe MR. This condition is associated with significant morbidity and mortality, making accurate diagnosis and management critical. In Europe, MR represents the second most prevalent valvular disorder requiring cardiac surgical intervention, highlighting its clinical significance in contemporary cardiology practice. MR is classified based on its underlying etiology and mechanism. Primary mitral regurgitation (PMR), or degenerative mitral regurgitation (DMR), results from intrinsic abnormalities of the mitral valve apparatus, such as degenerative changes in the valve leaflets, myxomatous infiltration, calcification of the annulus, or damage to the chordae tendineae. Secondary mitral regurgitation (SMR), or functional mitral regurgitation (FMR), typically occurs due to heart failure, left ventricular dilation, and altered coaptation of the mitral annulus. It arises when the mitral valve anatomy is normal, but abnormalities of the left ventricle or the left atrium disrupts the normal valvular function. Surgical mitral valve intervention remains the gold standard for many patients, particularly those with severe and symptomatic DMR. However, nearly 50% of the patients with MR cannot undergo surgery due to comorbidities, advance age or high surgical risk. For these patients, transcatheter therapies offer a viable alternative, focusing on leaflet or annulus repair, or valve replacement. The most widely used technique is leaflet approximation (mitral transcatheter edge-to-edge repair, M-TEER) with more than 150,000 implantations worldwide. The TEER technique is minimally invasive with low risks. Compared to surgical repair, TEER results in fewer complications and shorter hospital stays. Several TEER devices are available for MR treatment. Among them, the MitraClip device by Abbott Laboratories is the most widely adopted TEER device globally, while the PASCAL system by Edwards Lifesciences provides an alternative technology that may offer specific advantages in certain clinical scenarios. The X-ClipTM Mitral Valve Clip System and Steerable Guide System shares a similar concept with MitraClip and PASCAL systems but has unique features. It features a larger clamping area and employs a mechanical elastic clip design to ensure precise capture and grasping of leaflets. The system was initially studied in the First-in-Man feasibility study in China, which showed that TEER using the system is feasible and safe for the treating patients with moderate-to-severe and severe mitral regurgitation. Here, this clinical study aims to further evaluate the safety and performance of the X-ClipTM Mitral Valve Clip System and Steerable Guide System in European population with moderate-to-severe and severe degenerative mitral regurgitation who are at high surgical risk and have suitable mitral anatomy for TEER.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: To participate in this study, the patient must meet ALL of the following inclusion criteria: 1. 18 years of age or older, no gender limit; 2. New York Heart Association function class II, III or IV; 3. Moderate-to-severe or severe mitral valve regurgitation (grade≥3+) confirmed by transthoracic echocardiography or transesophageal echocardiography; 4. Patients with symptoms, or without symptoms but with left ventricular ejection fraction (LVEF) ≤ 60% or left ventricular end-systolic diameter (LVESD) ≥ 40 mm; 5. Patients are determined to be at a high risk for mitral valve surgery by cardiologists and should meet at least one of the following four criteria: 1. The American Society of Thoracic Surgeons (STS) predicted risk of mortality (PROM) is ≥ 6% for valve repair or is ≥ 8% for valve replacement; 2. Presence of ≥2 frailty indices (moderate to severe frailty); 3. Presence of ≥2 major organ dysfunctions that could not be improved after surgery; 4. Presence of other surgical high-risk comorbidities or factors as determined by the heart team. 6. Anatomically suitable for transcatheter mitral valve repair by edge-to-edge technique, can be treated by the investigational device, and transseptal catheterization and femoral vein access is determined to be feasible. 7. Patients who voluntarily participate in the study and sign the informed consent form (ICF), and are willing to undergo the required examinations and clinical follow-up visits. Exclusion Criteria: Patients will be excluded if ANY of the following conditions apply: 1. Patients who are unable to tolerate the treatment, including those with allergies or hypersensitivity to anticoagulant or antiplatelet agents; 2. Patients with contraindications to antithrombotic medication, or those with a history of cerebral hemorrhage, gastrointestinal hemorrhage, or hemorrhagic disorders within the past 3 months; 3. Patients known to have hypersensitivity or allergic reactions to nickel or titanium, cobalt, chromium, polyester, fluoropolymers, or contrast media; 4. Patients with active mitral valve endocarditis, rheumatic mitral valve disease, or mitral valve leaflet abnormalities (i.e. noncompliant, perforation) resulting from endocarditis or rheumatic heart disease; 5. Patients with active infections that significantly impact both the outcome of mitral valve transcatheter interventions and postoperative recovery; 6. Patients with intracardiac thrombus, vegetations, or masses identified by echocardiography; 7. Patients with coronary artery stenosis requiring revascularization, or those who have undergone coronary artery surgery within the past 30 days; 8. Patients with aortic stenosis or regurgitation requiring surgical intervention, as well as those with other cardiac conditions necessitating surgical treatment, as judged by clinicians; 9. Patients with unfavorable mitral valve anatomy for mitral valve clip placement, including but not limited to a mitral valve orifice area less than 4 cm²; 10. Patients with a history of heart transplantation, prior mitral valve surgery, or previous mitral valve transcatheter procedures; 11. Patients with severe pulmonary hypertension (pulmonary artery systolic pressure \> 70 mmHg, assessed by echocardiography or right heart catheterization, with right heart catheterization taking precedence in cases of concurrent measurement); 12. Patients with moderate-to-severe or severe right ventricular dysfunction as demonstrated by echocardiographic findings; 13. Patients with thrombi located in the inferior vena cava or femoral vein, presence of inferior vena cava filters, tortuous or obstructed venous anatomy, or other venous access limitations; 14. Patients unable to participate the 6-minute walk test; 15. Presence of diseases that may complicate the evaluation of treatment outcomes (e.g., coma, cancer, psychiatric disorders); 16. Pregnant or breastfeeding women, as well as women planning to become pregnant within the next 12 months; 17. Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator; 18. Patient is currently participating in another investigational drug or device clinical study; 19. Any other conditions deemed by the investigator to render the subject unsuitable for participation in the clinical study.

Outcomes

Primary Outcomes

Incidence of major adverse events (MAEs) within 30 days after operation

MAEs are defined as cardiovascular mortality, stroke, myocardial infarction, renal replacement therapy (e.g., dialysis), severe bleeding, and mitral valve reintervention (either transcatheter or surgical). Note: MAEs are defined per Mitral Valve Academic Research Consortium (MVARC). Severe bleeding is major, extensive, life-threatening or fatal bleeding defined by the Mitral Valve Academic Research Consortium.

Time frame: At pre-discharge, 30 days ± 7 days post-procedure

Clinical success rate

Clinical success is defined as freedom from mortality, reintervention for mitral valve dysfunction, and moderate-to-severe or severe mitral regurgitation (grade≥3+) at the 12-month postoperative follow-up. Note: \*Mitral severity is evaluated through transthoracic echocardiography (TTE) or transoesophageal echocardiography (TEE).

Time frame: At 12 months ± 30 days post-procedure

Secondary Outcomes

Incidence of major adverse events (MAEs)

Evaluation method: Evaluating and recording the number of subjects experiencing MAEs at 6 months ± 30 days and 12 months ± 30 days post-procedure. Calculation formula: Incidence of MAEs = (Number of subjects with MAEs / Total number of subjects) × 100%

Time frame: At 6 months ± 30 days post-procedure; 12 months ± 30 days post-procedure

All-cause mortality

Evaluation method: All-cause mortality is defined as death from any cause, regardless of its relationship to the investigational device. However, when a death occurs, the cause of death (cardiovascular-related or non-cardiovascular-related) should be determined. Deaths for which no clear cause can be determined are classified as cardiovascular-related. The number of all-cause mortality subjects is recorded at immediate post-procedure, and 7 days ± 5 days, 30 days ± 7 days, 6 months ± 30 days, 12 months ± 30 days, 24 months ± 60 days, 36 months ± 60 days, 48 months ± 60 days, and 60 months ± 60 days post-procedure. Calculation formula: All-cause mortality = (Number of all-cause mortality subjects / Total number of subjects) × 100%.

Time frame: From immediate post-procedure to the end of treatment at 5 years ± 60 days post-procedure

Cardiac mortality

Evaluation method: The number of cardiac mortality subjects is recorded at immediate post-procedure, and 7 days ± 5 days, 30 days ± 7 days, 6 months ± 30 days, 12 months ± 30 days, 24 months ± 60 days, 36 months ± 60 days, 48 months ± 60 days, and 60 months ± 60 days post-procedure. Calculation formula: Cardiac mortality = (Number of cardiac mortality subjects / Total number of subjects) × 100%.

Time frame: From immediate post-procedure to the end of treatment at 5 years ± 60 days post-procedure

Incidence of adverse events (AEs)

Evaluation method: The types, incidences (%), and frequencies (number of occurrences) of AEs are recorded during the study period.

Time frame: From immediate post-procedure to the end of treatment at 5 years ± 60 days post-procedure

Incidence of serious adverse events (SAEs)

Evaluation method: The types, incidences (%), and frequencies (number of occurrences) of SAEs are recorded during the study period.

Time frame: From immediate post-procedure to the end of treatment at 5 years ± 60 days post-procedure

Clinical success rate

Evaluation method: Assessing and recording the number of subjects who experience no mortality, no reintervention for mitral valve dysfunction, and no moderate-to-severe or severe mitral regurgitation (≥3+) at 30 days ± 7 days and 6 months ± 30 days post-procedure. Calculation formula: Clinical success rate = (Number of clinical success subjects / Total number of subjects) × 100%

Time frame: At 30 days ± 7 days post-procedure, 6 months ± 30 days post-procedure

Proportion of patients with New York Heart Association (NYHA) Function Class I or II

Evaluation method: Evaluating and recording the number of subjects with NYHA function class I or II at 30 days ± 7 days, 6 months ± 30 days and 12 months ± 30 days post-procedure. Calculation formula: Proportion of patients with NYHA Function Class I or II = (Number of subjects with NYHA function class I or II / Total number of subjects) × 100%

Time frame: At 30 days ± 7 days post-procedure; 6 months ± 30 days post-procedure; 12 months ± 30 days post-procedure

Incidence of heart failure hospitalization (HFH)

Evaluation method: Evaluating and recording the number of subjects experiencing HFH at 30 days ± 7 days, 6 months ± 30 days and 12 months ± 30 days post-procedure. Calculation formula: Incidence of HFH = (Number of subjects experiencing HFH / Total number of subjects) × 100%

Time frame: At 30 days ± 7 days post-procedure; 6 months ± 30 days post-procedure; 12 months ± 30 days post-procedure

Quality-of-life score

Evaluation method: Quality-of-life score is measured by Short-Form 36 Health Survey Questionnaire (SF-36) at 1-, 6-, and 12-months post-procedure and is compared with each patient's baseline scores.

Time frame: At 30 days ± 7 days post-procedure; 6 months ± 30 days post-procedure; 12 months ± 30 days post-procedure

Change in mean 6 min walking distance (M6WD)

Evaluation method: The change in M6WD is measured using the 6-minute walk test (6MWT) at 1-, 6-, and 12-months post-procedure and is compared with each patient's baseline distance.

Time frame: At 30 days ± 7 days post-procedure; 6 months ± 30 days post-procedure; 12 months ± 30 days post-procedure

Change of left ventricular function

Evaluation method: Left ventricular function is assessed using parameters including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD). Each parameter is measured at immediate post-procedure, and 7 days ± 5 days, 30 days ± 7 days, 6 months ± 30 days and 12 months ± 30 days post-procedure, and compared with each patient's baseline values.

Time frame: At immediate post-procedure; 7 days ± 5 days post-procedure; 30 days ± 7 days post-procedure; 6 months ± 30 days post-procedure; 12 months ± 30 days post-procedure

Change of mitral regurgitation degree

Evaluation method: The mitral regurgitation degree of each subject is assessed according to Annex VIII: Evaluation of Mitral Regurgitation Severity, at immediate post-procedure, and 7 days ± 5 days, 30 days ± 7 days, 6 months ± 30 days, 12 months ± 30 days post-procedure, 24 months ± 60 days post-procedure, 36 months ± 60 days post-procedure, 48 months ± 60 days post-procedure, and 60 months ± 60 days post-procedure. The results are compared with each patients' baseline degree.

Time frame: From immediate post-procedure to the end of treatment at 5 years ± 60 days post-procedure

A Clinical Study of X-Clip Mitral Valve Clip System and Steerable Guide System for Transcatheter Mitral Valve Repair of Degenerative Mitral Regurgitation

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts