Early Feasibility Study of the Cardiac Implants Percutaneous Ring Annuloplasty System

• ClinicalTrials.gov Identifier: NCT04890821
• Recruitment Status: Recruiting
• First Posted: May 18, 2021
• Last Update Posted: November 30, 2021
• Sponsor: Cardiac Implants LLC
• Information provided by (Responsible Party): Cardiac Implants LLC

Study Description

Brief Summary:

An early feasibility study to evaluate the safety and performance of 1) the transcatheter delivery and implantation of the Cardiac Implants (CI) annuloplasty ring and 2) the adjustment of the ring approximately 90 days following implantation in patients suffering from ≥ moderate functional tricuspid regurgitation (FTR).

Condition or disease	Intervention/treatment	Phase
Tricuspid Regurgitation Functional	Device: CI Percutaneous Ring Annuloplasty System	Not Applicable

Detailed Description:

An early feasibility, multi-center, prospective, single-arm, non-randomized study to assess the safety and performance of the CI Percutaneous Ring Annuloplasty System in patients suffering from ≥ moderate functional tricuspid regurgitation (FTR). Additional outcomes include short and long-term changes in echocardiographic, functional, and quality of life parameters post-adjustment.

The CI Ring Annuloplasty System is a percutaneous transcatheter repair device delivered by right heart catheterization through the right internal jugular vein. The System is designed to perform annuloplasty using a Ring Delivery System (RDS) to place a complete, flexible ring over the tricuspid annulus on the atrial side of the valve. Fluoroscopy and transesophageal echocardiography are used to guide and monitor the ring placement procedure.

After implantation, the ring becomes embedded within the fibrous tissue of the tricuspid annulus. Approximately 3 months following implantation, the ring is manually adjusted under echocardiographic and fluoroscopic imaging using an Adjustment Tool (AT) until desired reduction of the tricuspid annulus dimension is achieved. Following adjustment, the AT releases a fastener, securing the ring once optimal annular reduction is achieved.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Feasibility Study (EFS) of the Cardiac Implants Percutaneous Ring Annuloplasty System for the Treatment of Functional Tricuspid Regurgitation
• Estimated Study Start Date: December 2021
• Estimated Primary Completion Date: August 2022
• Estimated Study Completion Date: September 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: CI Percutaneous Ring Annuloplasty System; Patients treated with the CI Percutaneous Ring Annuloplasty System	Device: CI Percutaneous Ring Annuloplasty System; Percutaneous transcatheter implant and adjustment of the CI ring annuloplasty system.

Outcome Measures

Primary Outcome Measures :

1. Freedom from device or procedure-related mortality [ Time Frame: 30 days post-adjustment ]
   Freedom from mortality determined to be primarily caused by the device or procedure in the primary endpoint cohort. Events adjudicated by a Clinical Events Committee (CEC).

Secondary Outcome Measures :

1. Safety: Incidence of device or procedure-related major adverse events (MAE) [ Time Frame: 30, 60, and 90 days post-implant; 30 days, 3 months, 6 months, 12 months, and 2-5 years (annually) post-adjustment ]
   The incidence of MAEs determined to be primarily caused by the device or procedure. Events adjudicated by CEC.
2. Technical: Proportion of successful access, delivery, and retrieval device delivery system [ Time Frame: 30 days post-implant and 30 days post-adjustment ]
   The proportion of successful access, delivery, and retrieval of the device delivery system.
3. Technical: Proportion of successful deployment and positioning of the ring implant. [ Time Frame: 30 days post-implant and 30 days post-adjustment ]
   The proportion of successful deployment and correct/stable positioning of the ring implant.
4. Technical: Freedom from emergency surgery or reintervention [ Time Frame: 30 days post-implant and 30 days post-adjustment ]
   The proportion of subjects free from emergency surgery or reintervention casually related to the device or access procedure.
5. Technical: Rate of Successful Implants [ Time Frame: 30 days post-implant ]
   The proportion of subjects with successful ring implants.
6. Technical: Proportion of Successful Procedures [ Time Frame: 30 days post-implant and 30 days post-adjustment ]
   Proportion of successful procedures, as defined in Mitral Valve Academic Research Consortium (MVARC)
7. Technical: Number of device stakes embedded in tissue [ Time Frame: 30 days post-implant, 30 days post-adjustment, and 1 year post-adjustment ]
   Proportion of device stakes embedded in tissue vs. stakes remain embedded at follow-up, per subject, as assessed through multi-modality imaging (i.e. fluoroscopy, cine, TEE, and Cardiac CT) and evaluated by an independent Core Lab(s).
8. Mechanistic: Changes in TR Severity [ Time Frame: 30 and 90 days post-implant; and 30, 90, 180, and 1-2 years (annually) post-adjustment ]
   The changes in TR severity, characterized per the American Society of Echocardiography (ASE) guidelines, as compared to baseline, to be evaluated by independent Core Lab.
9. Mechanistic: Echocardiographic changes: Changes Tricuspid Valve (TV) Annular Diameter [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
   Changes in TV annular diameter as compared to baseline, determined via echocardiography.
10. Mechanistic: Echocardiographic changes: Changes in TV Area [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in TV area as compared to baseline, determined via echocardiography.
11. Mechanistic: Echocardiographic changes: Changes in Vena Contracta (VC) dimensions [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in VC dimensions as compared to baseline, determined via echocardiography.
12. Mechanistic: Echocardiographic changes: Changes in Proximal isovelocity surface area (PISA) effective regurgitant orifice area (EROA) [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in PISA EROA as compared to baseline, determined via echocardiography.
13. Mechanistic: Echocardiographic changes: Changes in Quantitive EROA [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in quantitative EROA as compared to baseline, determined via echocardiography.
14. Mechanistic: Echocardiographic changes: Changes in TV Regurgitant Volume [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in TV regurgitant volume as compared to baseline, determined via echocardiography.
15. Mechanistic: Echocardiographic changes: Changes in Right Atrium (RA) Dimensions [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in RA dimensions as compared to baseline, determined via echocardiography.
16. Mechanistic: Echocardiographic changes: Changes in Right Ventricle (RV) Dimensions [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in RV dimensions (cm) as compared to baseline, determined via echocardiography.
17. Mechanistic: Echocardiographic changes: Changes in Inferior Vena Cava (IVC) Dimensions [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in IVC dimensions as compared to baseline, determined via echocardiography.
18. Mechanistic: Echocardiographic changes: Changes in Tricuspid Annular Plane Systolic Excursion (TAPSE) [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in TAPSE as compared to baseline, determined via echocardiography.
19. Mechanistic: Echocardiographic changes: Changes in Left Atrium (LA) Dimensions [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in LA dimensions as compared to baseline, determined via echocardiography.
20. Mechanistic: Echocardiographic changes: Changes in Left Ventricle (LV) Dimensions [ Time Frame: 30 days, 90 days, 180 days, 1 year, and 2 years post-adjustment ]
    Changes in LV dimensions as compared to baseline, determined via echocardiography.
21. Functional: Changes in NYHA Classification [ Time Frame: 1 year post-adjustment ]
    Changes in New York Heart Association (NYHA) classification as compared to baseline.
22. Functional: Changes in Distance Walked for Exercise Tolerance [ Time Frame: 1 year post-adjustment ]
    Changes in distance walked, assessed by 6 Minute Walk Test
23. Functional: Changes in Quality of Life Scores and Sub-Domains [ Time Frame: 1 year post-adjustment ]
    Changes in quality of life overall score and sub-domains in comparison to baseline values as evaluated by the Kansas City Cardiomyopathy Questionnaire (KCCQ)

Other Outcome Measures:

1. Freedom from Heart Failure Events [ Time Frame: 30 days, 90 days, 180 days, and 1-5 years (annually) post-adjustment ]
   Freedom from heart failure events post-adjustment defined as a heart failure hospitalization, stratified by cardiac related vs. non-cardiac events compared to baseline.
2. Changes in Heart Failure Biomarkers [ Time Frame: 180 days, 1 year, and 2 years post-adjustment ]
   Changes in N-terminal (NT)-pro hormone BNP (NT-proBNP) levels as compared to baseline.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Moderate to severe functional tricuspid regurgitation (TR) defined by ASE guidelines and the European Association of Echocardiography guidelines.
2. Tricuspid valve annular diameter ≥ 40mm or > 21 mm/m2 as measured by baseline TTE in a 4-chamber view within 90 days prior to index implant procedure.
3. Age ≥ 18 years old at the time of enrollment.
4. New York Heart Associate Classification ≥ II.
5. Symptoms of right heart failure despite optimized medical therapy.
6. Multidisciplinary heart team (minimum of four physicians, including imaging, Structural Heart Disease Interventionalist, Heart Failure Cardiologist, and Cardiac Surgeon) agree that percutaneous tricuspid annuloplasty is a reasonable treatment.
7. Left Ventricular Ejection Fraction (LVEF) ≥ 30% within 90 days prior to index implant procedure
8. The subject has suitable anatomy for investigational device implantation as per imaging requirements.
9. The subject has read and signed the informed consent prior to study related procedures.
10. The subject is willing and able to comply with all required follow-up evaluations and assessments.

Exclusion Criteria:

1. Acute decompensated heart failure requiring hospital admission with 4 weeks of enrollment.
2. Severe RV dysfunction as assessed by echocardiography.
3. Primary (organic) tricuspid pathology (e.g. rheumatic, congenital, infective, etc.).
4. Currently participating in another investigational drug or device study.
5. Systolic pulmonary arterial pressure (sPAP) > 70 mmHg as measured by Transthoracic Echocardiography (TTE).
6. Subject requiring another cardiac procedure in the framework of the index procedure; subject requiring a percutaneous procedure within 30 days before or after the procedure or a cardiac surgical procedure within 3 months before or after the procedure.
7. Tricuspid valve stenosis.
8. Aortic, mitral and/or pulmonic valve stenosis and/or regurgitation more than moderate.
9. Intra-cardiac thrombus, mass or vegetation requiring active treatment.
10. Prior tricuspid repair or tricuspid replacement.
11. Known allergy to contrast media, stainless steel or nitinol that cannot be adequately pre-medicated.
12. History of cardiac transplantation.
13. Contraindication to Transthoracic/Transesophageal Echocardiography (TTE/TEE).
14. Endocarditis or severe infection within 12 months of scheduled implant procedure.
15. Myocardial Infarction (MI), percutaneous coronary intervention (PCI), or known unstable angina within the 60 days prior to the index procedure.
16. Cerebro-Vascular Accident within the previous 3 months.
17. Hemodynamic instability or on IV inotropes.
18. Contraindication to anticoagulant therapy and dual antiplatelet therapy.
19. Documented history of bleeding diathesis, hypercoagulable or active peptic ulcer or gastrointestinal bleeding within 3 months of scheduled implant procedure.
20. Severe renal impairment or on dialysis.
21. Any condition that, in the opinion of the investigator, may render the subject unable to complete the study (e.g. life expectancy < 1 year), or lead to difficulties for subject compliance with study requirements.
22. Acute anemia.
23. Chronic Oral Steroid Use ≥ 6 months.
24. Pregnant or lactating female of childbearing potential with a positive pregnancy test 24 hours before any study-related radiation exposure.
25. Pulmonary embolism within the last 6 months.
26. Tricuspid Valve Tethering distance > 10 mm.
27. Presence of transvalvular pacemaker or defibrillator leads which are determined as immobile or interfering with the procedure, as evaluated by echocardiography.
28. Inadequate TEE acoustic window for appropriate visualization of the tricuspid valve that is required for guiding the index implant procedure.
29. Contra-indicated for blood transfusion or refuses transfusion.
30. Patient undergoing emergency treatment.
31. Patient without appropriate jugular access.

Contacts and Locations

Contacts

Contact: Nodar Kipshidze, MPH; 1-917-370-6247; Nodar@cardiac-implants.com

Locations

United States, New Jersey

Hackensack University Medical Center; Not yet recruiting

Hackensack, New Jersey, United States, 07601

Contact: Peter Canino 551-996-3775 Peter.Canino@hmhn.org

Principal Investigator: Tilak Pasala, MD

United States, New York

Weill Cornell Medicine-New York Presbyterian Hospital; Recruiting

New York, New York, United States, 10065

Contact: Dolores Reynolds 212-746-4617 Dtr2001@med.cornell.edu

Principal Investigator: Mark Reisman, MD

Sponsors and Collaborators

Cardiac Implants LLC

Investigators

• Study Director: Nodar Kipshidze, MPH; Cardiac Implants LLC

More Information

• Responsible Party: Cardiac Implants LLC
• ClinicalTrials.gov Identifier: NCT04890821
• Other Study ID Numbers: CLP-100
• First Posted: May 18, 2021
• Last Update Posted: November 30, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Cardiac Implants LLC:

Tricuspid Valve; Annular Dilatation; Annuloplasty; Tricuspid Valve Repair

Additional relevant MeSH terms:

Tricuspid Valve Insufficiency; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases