TRILUMINATE Pivotal Trial

• ClinicalTrials.gov Identifier: NCT03904147
• Recruitment Status: Active, not recruiting
• First Posted: April 5, 2019
• Results First Posted: March 27, 2024
• Last Update Posted: April 8, 2024
• Sponsor: Abbott Medical Devices
• Information provided by (Responsible Party): Abbott Medical Devices

Tracking Information

• First Submitted Date: April 3, 2019
• First Posted Date: April 5, 2019
• Results First Submitted Date: January 9, 2024
• Results First Posted Date: March 27, 2024
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: August 21, 2019
• Actual Primary Completion Date: November 18, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2024)

• For Randomized Cohort: Hierarchical Composite of All-cause Death or Tricuspid Valve Surgery, Heart Failure Hospitalizations, and KCCQ Improvement [ Time Frame: 12 Months ]
  Analysis of hierarchical composite of all-cause death or tricuspid valve surgery, heart failure hospitalizations, and KCCQ improvement of at least 15 points was performed in ITT population using Finkelstein-Schoenfeld method. A win ratio was also calculated to descriptively quantify the magnitude of treatment benefits. The win ratio is calculated as the ratio of the number of wins in Device versus Control patients. The primary analysis population consisted of 175 Device patients and 175 Control patients, resulting in 30,625 Device-Control patient pairs (i.e., 175 × 175).
• For Single-Arm Cohort: Rate of Survival Through 12 Months With a Quality of Life Improvement (Assessed Using KCCQ Overall Score) of at Least 10 Points Compared to Baseline. [ Time Frame: 12 months ]
  This outcome will be assessed as the percentage of subjects meeting the definition of the endpoint.

• Original Primary Outcome Measures (submitted: April 3, 2019): Hierarchical composite of all-cause mortality or tricuspid valve surgery, heart failure hospitalizations, and quality of life improvement assessed using the KCCQ [ Time Frame: 12 Months ]

Current Secondary Outcome Measures (submitted: March 26, 2024)

• For Randomized Cohort - Device Group Only: Rate of Kaplan-Meier Estimate (SE) of Freedom From Major Adverse Events (MAE) Occurring Within 30 Days Post-procedure [ Time Frame: 30 Days ]
  Freedom from major adverse events (MAE) was assessed in the Attempted Procedure population (n=172). MAEs included cardiovascular mortality, new onset renal failure, endocarditis requiring surgery, and non-elective cardiovascular surgery for TriClip device-related AE post-index procedure.
• For Randomized Cohort: Change in Quality of Life as Assessed by KCCQ Score [ Time Frame: 12 months minus baseline ]
  The mean change in KCCQ score between 12 months and baseline in the Device and Control groups will be compared, while adjusting for the baseline KCCQ score. The primary analysis for this endpoint imputed a KCCQ score of 0 at 12-month visit for all subjects who experienced a heart failure related cardiovascular death or received tricuspid valve surgery prior to completing 12-month follow-up. All KCCQ scores are scaled from 0 (worst) to 100 (best possible status), where the higher score reflects a better health status.
• For Randomized Cohort: Tricuspid Regurgitation Reduction to Moderate or Less at 30-Day Visit [ Time Frame: 30 Days ]
  The percentage of subjects with tricuspid regurgitation reduced to moderate or less at 30-day visit in the Device Group will be compared with that in the Control Group. Tricuspid regurgitation severity will be graded on a 5-point scale: trace/mild, moderate, severe (severe 3), massive (severe 4), and torrential (severe 5), which has frequently been used in recent interventional tricuspid studies to categorize tricuspid regurgitation severity. This grading system follows the 2017 ASE guidelines (Zoghbi WA, Adams D, Bonow RO et al. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 2017;30:303-371.), and further stratifies the traditional "severe" category into severe (Severe 3), massive (Severe 4), and torrential (Severe 5).
• For Randomized Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 12 Months [ Time Frame: 12 Months ]
  The primary analysis for this endpoint imputed a 6MWT distance of 0 meters for all subjects who experienced a heart failure related cardiovascular death or received tricuspid valve surgery prior to completing 12-month follow-up. Subjects who were unable to exercise due to cardiac reasons were also assigned a 6MWT distance of 0 meters at 12-month follow-up. Other subjects with missing 6MWT distance at either baseline or 12-month follow-up were excluded from the analysis.
• For Single-Arm Cohort: The Percentage of Subjects With TR Reduction by at Least 1 Grade at 30-Day Follow-up [ Time Frame: 30 days ]
• For Single-Arm Cohort: Rate of Freedom From MAE Through 30 Days [ Time Frame: 30 days ]
  Freedom from MAE occurring after procedure attempt (femoral vein puncture) at 30 days. Components of MAE consist of Cardiovascular Mortality, New Onset Renal Failure, Endocarditis Requiring Surgery, and Non-Elective Cardiovascular Surgery for TriClip device-related AE post-index procedure.
• For Single-Arm Cohort: Change in 6 Minute Walk Test (6MWT) From Baseline to 12 Months [ Time Frame: 12 months ]
  This analysis imputed a 6MWT distance of 0 meters for all subjects who were unable to exercise due to cardiac reasons. However, there were no subjects unable to exercise due to cardiac reasons and therefore no imputation was performed. Subjects with missing 6MWT distance at either baseline or 12-month follow-up were excluded from the analysis.
• Recurrent HF Hospitalizations at 24 Months [ Time Frame: 24 months ]
  H0: HR(24M)>1; H1: HR(24M)≤1
• Freedom From All-cause Mortality, Tricuspid Valve Surgery, and Tricuspid Valve Intervention at 24 Months [ Time Frame: 24 months ]
  H0: Survival curves of the two groups through 24 months are the same. H1: Survival curves of the two groups through 24 months are different.

Original Secondary Outcome Measures (submitted: April 3, 2019)

• TR Reduction to moderate or less [ Time Frame: 30 Days ]
• Freedom from major adverse events (MAE) occurring after procedure attempt [ Time Frame: 30 Days ]
• Change in KCCQ [ Time Frame: 12 Months ]
• Change in 6MWT [ Time Frame: 12 Months ]

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

Descriptive Information

• Brief Title: TRILUMINATE Pivotal Trial
• Official Title: Clinical Trial to Evaluate Cardiovascular Outcomes In Patients Treated With the Tricuspid Valve Repair System Pivotal
• Brief Summary: The primary objective of this trial is to demonstrate the safety and effectiveness of the TriClip device in improving clinical outcomes in symptomatic patients with severe tricuspid regurgitation (TR), who are at intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery. This randomized controlled trial will compare the investigational device (TriClip device) to Control (Medical Therapy).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Tricuspid Regurgitation

Intervention

Device: TriClipTM Device

Transcatheter TriClip placement in the tricuspid valve to repair the valve and correct regurgitation

Study Arms

• Experimental: Randomized - Device Group
  Subjects will undergo TriClip implantation and will continue to be managed on medical therapy, per physician discretion
  Intervention: Device: TriClipTM Device
• Active Comparator: Randomized - Control Group
  Subjects will continue to be managed on medical therapy, per physician discretion
  Intervention: Device: TriClipTM Device
• Experimental: Single Arm Group
  Subjects will receive the TriClip device and will continue to be managed on medical therapy, per physician discretion.
  Intervention: Device: TriClipTM Device
• Experimental: Continued Access Study (CAS)
  Subjects will undergo TriClip implantation and will continue to be managed on medical therapy, per physician discretion
  Intervention: Device: TriClipTM Device

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 3, 2024): 572
• Original Estimated Enrollment (submitted: April 3, 2019): 700
• Estimated Study Completion Date: April 2029
• Actual Primary Completion Date: November 18, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• In the judgment of the site local heart team, subject has been adequately treated per applicable standards (including medical management) and stable for at least 30 days as follows:

  • Optimized medical therapy for treatment of TR (e.g. diuretics).
  • Medical and/or device therapy, for mitral regurgitation, atrial fibrillation, coronary artery disease and heart failure.
  • The Eligibility Committee will confirm that the subject has been adequately treated medically.
• Subject is symptomatic with Severe TR despite being optimally treated as described above. TR severity is determined by the assessment of a qualifying TTE and confirmed by the ECL. The ECL will also request a TEE to confirm TR etiology. Note: If any cardiac procedure(s) occur after eligibility was determined, TR severity will need to be re-assessed 30 days after the cardiac procedure(s).
• The cardiac surgeon of the site local heart team concur that the patient is at intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery.
• New York Heart Association (NYHA) Functional Class II, III or ambulatory class IV
• In the judgment of the TriClip(TM) implanting Investigator, femoral vein access is determined to be feasible and can accommodate a 25 Fr catheter.
• Age ≥18 years at time of consent.
• Subject must provide written informed consent prior to any trial related procedure.

Exclusion Criteria:

• Systolic pulmonary artery pressure (sPAP) > 70 mmHg or fixed pre-capillary pulmonary hypertension as assessed by right heart catheterization (RHC)
• Severe uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 180 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 110 mm Hg
• Any prior tricuspid valve procedure that would interfere with placement of the TriClip(TM) device
• Indication for left-sided (e.g. severe aortic stenosis, severe mitral regurgitation) or pulmonary valve correction prior 60 days. Note: Patients with concomitant Mitral and tricuspid valve disease will have the option of getting their MR treated, and wait 60 days prior to being reassessed for the trial.
• Pacemaker or ICD leads that would prevent appropriate placement of the TriClip(TM) clip.
• Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg as measured by the ECL
• Left Ventricular Ejection Fraction (LVEF) ≤20%

• Tricuspid valve leaflet anatomy which may preclude clip implantation, proper clip positioning on the leaflets or sufficient reduction in TR. This may include:

  • Evidence of calcification in the grasping area
  • Presence of a severe coaptation defect (> 2cm) of the tricuspid leaflets
  • Severe leaflet defect(s) preventing proper device placement
  • Ebstein Anomaly - Identified by having a normal annulus position while the valve leaflets are attached to the walls and septum of the right ventricle.
• Tricuspid valve anatomy not evaluable by TTE and TEE
• Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e. noncompliant, perforated).
• MI or known unstable angina within prior 30 days
• Percutaneous coronary intervention within prior 30 days
• Hemodynamic instability defined as systolic pressure < 90 mmHg with or without afterload reduction, cardiogenic shock or the need for inotropic support or intra-aortic balloon pump or other hemodynamic support device.
• Cerebrovascular Accident (CVA) within prior 90 days
• Chronic dialysis
• Bleeding disorders or hypercoagulable state
• Active peptic ulcer or active gastrointestinal (GI) bleeding

• Contraindication, allergy or hypersensitivity to dual antiplatelet and anticoagulant therapy.

  • Note: Contraindication to either antiplatelet or anticoagulant therapy (individually not both therapies) is not an exclusion criterion.
• Ongoing infection requiring current antibiotic therapy (if temporary illness, patients may enroll 30 days after discontinuation of antibiotics with no active infection).
• Known allergy or hypersensitivity to device materials
• Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or vegetation.
• Life expectancy of less than 12 months
• Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.
• Subject is currently participating in another clinical investigation for valvular heart disease(s).
• Pregnant or nursing subjects and those who plan pregnancy during the clinical investigation follow-up period. Female subjects of child-bearing potential are required to have a negative pregnancy test done within 7 days of the baseline visit per site standard test. Female patients of childbearing potential should be instructed to use safe contraception (e.g., intrauterine devices, hormonal contraceptives: contraceptive pills, implants, transdermal patches hormonal vaginal devices, injections with prolonged release.) It is accepted, in certain cases, to include subjects having a sterilized regular partner or subjects using a double barrier contraceptive method.
• Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, Italy, Spain, United States
• Removed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT03904147
• Other Study ID Numbers: ABT-CIP-10249
• 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: Abbott Medical Devices
• Original Responsible Party: Same as current
• Current Study Sponsor: Abbott Medical Devices
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Erin Spinner, PhD; Abbott Structural Heart
• Principal Investigator: David Adams, MD; Icahn School of Medicine at Mount Sinai
• Principal Investigator: Paul Sorajja, MD; Allina Health System

• PRS Account: Abbott Medical Devices
• Verification Date: April 2024