Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial (CLASP IID/IIF)

• ClinicalTrials.gov Identifier: NCT03706833
• Recruitment Status: Recruiting
• First Posted: October 16, 2018
• Last Update Posted: March 2, 2023
• Sponsor: Edwards Lifesciences
• Information provided by (Responsible Party): Edwards Lifesciences

Tracking Information

• First Submitted Date: October 10, 2018
• First Posted Date: October 16, 2018
• Last Update Posted Date: March 2, 2023
• Actual Study Start Date: November 30, 2018
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2021)

• PASCAL is not inferior to MitraClip with respect to the proportion of patients with major adverse events (MAE). The primary safety endpoint is a composite of Major Adverse Events (MAEs). [ Time Frame: 30 days. ]
• PASCAL is not inferior to Mitraclip with respect to the proportion of patients with MR severity reduction as measured by echocardiography using a scale of 0-4+ for the CLASP IID Cohort. [ Time Frame: 6 months ]
• PASCAL is not inferior to Mitraclip with respect to the time to first heart failure hospitalization or death for the CLASP IIF Cohort only. [ Time Frame: From date of randomization until date of first heart failure hospitalization or death, through 5 year follow-up ]

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: February 26, 2021)

• Rates of various adverse events [ Time Frame: 6 months; 12 months ]
  Rates of various adverse events at 6 and 12 months
• Functional Improvement (increase in 6 minute walk test in meters) [ Time Frame: 30 days , 6 months, 1 year ]
  Increase in 6 minute walk test in meters
• Functional improvement (quality of life) as assessed using the Kansas City Cardiomyopathy Questionnaire through 2 years [ Time Frame: 30 days , 6 months, 1 year, 2 year ]
  Number of points of improvement on a scale of 0-100 in Kansas City Cardiomyopathy Questionnaire, with higher scores associated with higher Quality of Life
• Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (SF-36) questionnaire through 2 years [ Time Frame: 30 days, 6 months, 1 year, 2 year ]
  Number of points of improvement on a scale of 0-100 in Short Form Health Survey (SF-36) questionnaire, with higher totals associated with higher Quality of Life
• Functional improvement (quality of life) as assessed by number of points of improvement on the Short Form Health Survey (EQ-5D-5L) questionnaire through [ Time Frame: 30 days, 6 months, 1 year, 2 year ]
  Number of points of improvement on a scale of 1-100 in Short Form Health Survey (EQ-5D-5L) questionnaire, with higher totals associated with higher Quality of Life

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Edwards PASCAL CLASP IID/IIF Pivotal Clinical Trial
• Official Title: Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial (CLASP IID/IIF): A Prospective, Multicenter, Randomized, Controlled Pivotal Trial to Evaluate the Safety and Effectiveness of Transcatheter Mitral Valve Repair With the Edwards PASCAL Transcatheter Valve Repair System Compared to Abbott MitraClip in Patients With Mitral Regurgitation
• Brief Summary: To establish the safety and effectiveness of the Edwards PASCAL Transcatheter Valve Repair System in patients with degenerative mitral regurgitation (DMR) who have been determined to be at prohibitive risk for mitral valve surgery by the Heart Team, and in patients with functional mitral regurgitation (FMR) on guideline directed medical therapy (GDMT)

Detailed Description

A prospective, multicenter, randomized, controlled pivotal trial to evaluate the safety and effectiveness of transcatheter mitral valve repair with the Edwards PASCAL Transcatheter Valve Repair System compared to Abbott MitraClip in patients with degenerative mitral regurgitation (DMR) who have been determined to be at prohibitive risk for mitral valve surgery by the Heart Team, and in patients with functional mitral regurgitation (FMR) on guideline directed medical therapy (GDMT)

Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 5 years.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Degenerative Mitral Valve Disease
• Mitral Regurgitation
• Mitral Insufficiency
• Functional Mitral Regurgitation

Intervention

• Device: Edwards PASCAL System
  Transcatheter mitral valve repair with the Edwards PASCAL System
  Other Name: Transcatheter Mitral Valve repair (TMVr)
• Device: Abbott Mitraclip System
  Transcatheter mitral valve repair with the Abbott Mitraclip System
  Other Name: Transcatheter Mitral Valve repair (TMVr)

Study Arms

• Experimental: Edwards PASCAL System - CLASP IID
  Transcatheter mitral valve repair with the Edwards PASCAL System in patients with degenerative mitral regurgitation
  Intervention: Device: Edwards PASCAL System
• Active Comparator: Abbott Mitraclip System - CLASP IID
  Transcatheter mitral valve repair with the Abbott Mitraclip System in patients with degenerative mitral regurgitation
  Intervention: Device: Abbott Mitraclip System
• Experimental: Edwards PASCAL System - CLASP IIF
  Transcatheter mitral valve repair with the Edwards PASCAL System in patients on guideline directed medical therapy with functional mitral regurgitation
  Intervention: Device: Edwards PASCAL System
• Active Comparator: Abbott Mitraclip System - CLASP IIF
  Transcatheter mitral valve repair with the Abbott Mitraclip System in patients on guideline directed medical therapy with functional mitral regurgitation
  Intervention: Device: Abbott Mitraclip System
• Experimental: Edwards PASCAL System - Single-Arm Registry
  Transcatheter mitral valve repair with the Edwards PASCAL System in patients with mitral regurgitation who were deemed non-randomizable by a central screening committee (CSC) due to complex anatomical features described in the current MitraClip Instructions for Use (IFU) but were considered suitable for the PASCAL system.
  Intervention: Device: Edwards PASCAL System

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 8, 2023): 1247
• Original Enrollment: Not Provided
• Estimated Study Completion Date: January 31, 2028
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eighteen (18) years of age or older
• Patient is able and willing to give informed consent and follow protocol procedures, and comply with follow-up visit requirements.
• Patient is determined to be at prohibitive risk for mitral valve surgery by the heart team (CLASP IID cohort only).
• Patient is on stable heart failure medications/Guideline Directed Medical Therapy (CLASP IIF cohort only)
• Patient is determined to be a candidate for transcatheter mitral valve repair by the heart team for both PASCAL and MitraClip
• Mitral regurgitation (3+ to 4+) by echo
• Suitable valve and regurgitant jet morphology
• Elevated corrected BNP > 400 pg/ml or corrected NT-pro BNP of > 900 pg/ml or heart failure hospitalization within the past 12 months (CLASP IIF cohort only)
• LVEF ≥ 20% (and ≤ 50%; CLASP IIF cohort only)

Exclusion Criteria:

• Patient in whom a TEE is contraindicated or screening TEE is unsuccessful
• Mitral valve anatomy which may preclude proper PASCAL or MitraClip access, use and/or deployment or sufficient reduction in mitral regurgitation
• Patient with refractory heart failure requiring advanced intervention (i.e. left ventricular assist device, Status ≤5 heart transplantation) (ACC/AHA Stage D heart failure)
• Clinically significant, untreated coronary artery disease
• Recent stroke
• Other severe valve disorders requiring intervention
• Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months
• Any prior mitral valve surgery or transcatheter mitral valve procedure (excluding chordal replacement or surgical annuloplasty repair)
• Severe tricuspid regurgitation or tricuspid valve disease requiring surgery
• Active rheumatic heart disease or rheumatic etiology for MR
• Severe aortic stenosis or regurgitation
• Known history of untreated, severe carotid stenosis
• Recent deep vein thrombosis (DVT) or pulmonary embolism (PE)
• Severe COPD
• Pregnant or planning pregnancy within next 12 months. Note: Female patients of childbearing potential need to have a negative pregnancy test performed within 14 days prior to intervention and be adherent to an accepted method of contraception
• Concurrent medical condition with a life expectancy of less than 12 months in the judgment of the Investigator
• Patient is currently participating in another investigational biologic, drug or device clinical study where the primary study endpoint was not reached at time of enrollment
• Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including patients under guardianship

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Edwards TMTT Clinical Affairs; (949) 250-2500; TMTT_Clinical@edwards.com

• Listed Location Countries: Canada, Germany, Switzerland, United States

Administrative Information

• NCT Number: NCT03706833
• Other Study ID Numbers: 2018-07
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Edwards Lifesciences
• Original Responsible Party: [Redacted]
• Current Study Sponsor: Edwards Lifesciences
• Original Study Sponsor: [Redacted]
• Collaborators: Not Provided

Investigators

• Principal Investigator: Scott Lim, MD; University of Virginia
• Principal Investigator: Robert Smith, MD; The Heart Hospital Baylor Plano
• Principal Investigator: Linda Gillam, MD; Morristown Medical Center
• Principal Investigator: Vinod Thourani, MD; Piedmont Healthcare
• Principal Investigator: Paul Grayburn, MD; The Heart Hospital Baylor Plano
• Principal Investigator: Brian K Whisenant, MD; Intermountain Medical Center
• Principal Investigator: Jörg Hausleiter, MD; LMU München, Campus Gorsshadern
• Principal Investigator: Ralph Stephan von Bardeleben, MD; / Universitätsmedizin Mainz- Zentrum für Kardiologie

• PRS Account: Edwards Lifesciences
• Verification Date: March 2023