Clinical trial NCT04482062: TRISCEND II Pivotal Trial
Official title: Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Tricuspid Valve Regurgitation
Tricuspid Valve Insufficiency
Tricuspid Valve Disease
Heart Valve Diseases
Cardiovascular Diseases
Heart Failure
Lead sponsor: Edwards Lifesciences
Sponsor class: INDUSTRY
First posted: 2020-07-22
Enrollment: 1070
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pivotal trial to evaluate the safety and effectiveness of the Edwards EVOQUE tricuspid valve replacement system

Detailed description: The study is a prospective, multi-center, randomized controlled pivotal clinical trial to evaluate the safety and effectiveness of the EVOQUE System with optimal medical therapy (OMT) compared to OMT alone in the treatment of patients with at least severe tricuspid regurgitation. Subjects will be followed at discharge, 30 days, 3 months, 6 months and annually through 5 years.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Despite medical therapy (OMT) per the local Heart Team, patient has signs of TR, symptoms from TR, or prior heart failure hospitalization from TR. Patient must be on OMT per the local heart team at the time of TR assessment for trial eligibility (TTE). OMT includes stable oral diuretic medications, unless patient has a documented history of intolerance.
* Functional and/or degenerative TR graded as at least severe on a transthoracic echocardiogram (assessed by the echo core lab using a 5-grade classification)
* The Local Heart Team determines that the patient is appropriate for transcatheter tricuspid valve replacement
* Patient is willing and able to comply with all study evaluations and provides written informed consent.

Exclusion Criteria:

* Anatomy precluding proper device delivery, deployment and/or function
* LVEF \< 25%
* Evidence of severe right ventricular dysfunction
* Any of the following pulmonary pressure parameters:

  1. PASP \>60 mmHg by echo Doppler (unless RHC demonstrates PASP ≤70 mmHg)
  2. PASP \>70 mmHg by RHC
  3. PVR \>5 Wood units by RHC (unless PVR ≤5 Wood units and systolic BP \>85 mmHg after vasodilator challenge)
* Previous tricuspid surgery or intervention
* Presence of trans-tricuspid pacemaker or defibrillator lead with any of the following:

  1. Implanted in the RV within the last90 days
  2. Patient is pacemaker dependent5 on trans-tricuspid lead without alternative pacing option
  3. Has delivered appropriate ICD therapy
* Severe aortic, mitral and/or pulmonic valve stenosis and/or regurgitation.
* Active endocarditis within the last 90 days or infection requiring antibiotic therapy (oral or intravenous) within the last 14 days
* Hemodynamically significant pericardial effusion
* Significant intra-cardiac mass, thrombus, or vegetation.
* Clinically significant, untreated coronary artery disease requiring revascularization, evidence of acute coronary syndrome, recent myocardial infarction within the last 30 days.
* Any of the following cardiovascular procedures:

  1. Percutaneous coronary, intracardiac, or endovascular intervention within the last 30 days
  2. Carotid surgery within the last 30 days
  3. Direct current cardioversion within the last 30 days
  4. Leadless RV pacemaker implant within the last 30 days
  5. Cardiac surgery within the last 90 days
* Known history of untreated severe symptomatic carotid stenosis (\>50% by ultrasound) or asymptomatic carotid stenosis (\>70% by ultrasound)
* Need for emergent or urgent surgery for any reason, any planned cardiac surgery within the next 12 months (365days), or any planned percutaneous cardiac procedure within the next 90 days
* Hypotension (systolic pressure \<90 mmHg) or requirement for inotropic support or hemodynamic support within the last 30 days
* Patient with refractory heart failure requiring or which required advanced intervention (i.e. left ventricular assist device, transplantation) (ACC/AHA/ESC/EACTS Stage D heart failure)
* Deep vein thrombosis (DVT) or pulmonary embolism (PE) in the last 6 months (180 days)
* Stroke within the last 90 days
* Modified Rankin Scale ≥ 4 disability
* Severe renal insufficiency with estimated glomerular filtration rate (eGFR) ≤ 25 mL/min/1.73m2 or requiring chronic renal replacement therapy.
* Patients with hepatic insufficiency or cirrhosis with Child-Pugh score class C
* Patient is oxygen-dependent or requires continuous home oxygen
* Chronic anemia with transfusion dependency or Hgb \< 9 g/dL not corrected by transfusion
* Unable to walk at least 100 meters in a 6-minute walk test
* Thrombocytopenia (Platelet count \< 75,000/mm3) or thrombocytosis (Platelet count \> 750,000/mm3)
* Known bleeding or clotting disorders or patient refuses blood transfusion
* Active gastrointestinal (GI) bleeding within the last 90 days
* Pregnant, breastfeeding, or planning pregnancy within the next 12 months (365 days).
* Patients in whom (any of the following):

  1. TEE is contraindicated or cannot be completed
  2. tricuspid valve anatomy is not evaluable by TTE or TEE
* In the opinion of the investigator, access to and through the femoral vein/IVC with a guide sheath and delivery catheter is deemed not feasible (e.g. occluded femoral veins, occluded or thrombosed IVC filter)
* Untreatable hypersensitivity or contraindication to any of the following: all antiplatelets, all anticoagulants, nitinol alloys (nickel and titanium), bovine tissue, glutaraldehyde, or contrast media
* Currently participating in another investigational biologic, drug or device study
* Co-morbid condition(s) that, in the opinion of the Investigator, limit life expectancy to \< 12 months (365 days).
* Presence of infiltrative cardiomyopathy or valvulopathy (including carcinoid, amyloidosis, sarcoidosis, hemochromatosis) or significant uncorrected congenital heart disease (including but not limited to hemodynamically significant atrial septal defect, RV dysplasia, and arrhythmogenic RV)
* Any condition, in the opinion of the investigator, making it unlikely the patient will be able to complete all protocol procedures and follow-ups
* Other medical, social, or psychological conditions that preclude appropriate consent and follow-up, including patients under guardianship
* Any patient considered to be vulnerable

Primary outcomes:
measure: Randomized Cohort: Tricuspid Regurgitation (TR) grade reduction
timeFrame: 6 months
measure: Randomized Cohort: Hierarchical composite endpoint including: Kansas City Cardiomyopathy Questionnaire (KCCQ) improvement, New York Heart Association (NYHA) functional class improvement, and 6-minute walk test distance improvement
timeFrame: 6 months
measure: Randomized Cohort: Rate of Major Adverse Events (MAE)
timeFrame: 30 days
measure: Randomized Cohort: Hierarchical composite endpoint: all-cause mortality, RVAD implantation or heart transplant, tricuspid valve intervention, heart failure hospitalizations, KCCQ improvement, NYHA functional class improvement, and 6MWD improvement
timeFrame: 1 year
measure: Continued Access Study: Rate of Major Adverse Events (MAE)
timeFrame: 30 days
measure: Continued Access Study: Tricuspid Regurgitation (TR) grade reduction to moderate, mild, or none/trace
timeFrame: 6 months
measure: Continued Access Study: Quality of Life (QOL) as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: 6 months
measure: Continued Access Study: New York Heart Association (NYHA) functional class
timeFrame: 6 months
measure: Continued Access Study: 6MWD
timeFrame: 6 months
measure: Continued Access Study: All-cause mortality
timeFrame: 1 year
measure: Continued Access Study: Durable right ventricular assist device (RVAD) implantation or heart transplant
timeFrame: 1 year
measure: Continued Access Study: Total number of patients requiring tricuspid valve surgery or percutaneous tricuspid intervention
timeFrame: 1 year
measure: Continued Access Study: Annualized rate of heart failure hospitalizations
timeFrame: 1 year
measure: Continued Access Study: Quality of Life (QOL) as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: 1 year
measure: Continued Access Study: New York Heart Association (NYHA) functional class
timeFrame: 1 year
measure: Continued Access Study: 6MWD
timeFrame: 1 year
Secondary outcomes:
measure: Randomized cohort: Tricuspid Regurgitation (TR) grade reduction
timeFrame: Time Frame: Discharge (assessed up to 7 days post procedure)
measure: Randomized cohort: All-Cause Mortality
timeFrame: 1 year, annually through 5 years
measure: Randomized cohort: Heart failure hospitalizations
timeFrame: 1 year, annually through 5 years
measure: Randomized cohort: Non-elective tricuspid valve re-intervention (percutaneous or surgical)
timeFrame: 1 year, annually through 5 years
measure: Randomized cohort: Durable RVAD implantation or heart transplant
timeFrame: 1 year, annually through 5 years
measure: Randomized cohort: Need for paracentesis
timeFrame: 1 year, annually through 5 years
measure: Randomized cohort: Reduction in TR grade by at least one grade
timeFrame: 1 year
measure: Randomized cohort: Reduction in New York Heart Association (NYHA) functional class by at least one grade
timeFrame: 1 year
measure: Randomized cohort: Change in Quality of Life (QOL) as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline
timeFrame: 1 year
measure: Randomized cohort: Death and heart failure hospitalization
timeFrame: 1 year
measure: Randomized cohort: All-cause hospitalizations
timeFrame: 1 year
measure: Randomized cohort: All-cause mortality
timeFrame: 1 year
measure: Randomized cohort: Change in 6MWD from baseline
timeFrame: 1 year
measure: Roll-in cohort: Tricuspid Regurgitation (TR) grade reduction
timeFrame: Time Frame: Discharge (assessed up to 7 days post procedure)
measure: Roll-in cohort: All-cause mortality
timeFrame: 1 year, annually through 5 years
measure: Roll-in cohort: Heart failure hospitalizations
timeFrame: 1 year, annually through 5 years
measure: Roll-in cohort: Non-elective tricuspid valve re-intervention (percutaneous or surgical)
timeFrame: 1 year, annually through 5 years
measure: Roll-in cohort: Durable RVAD implantation or heart transplant
timeFrame: 1 year, annually through 5 years
measure: Roll-in cohort: Need for paracentesis
timeFrame: 1 year, annually through 5 years
measure: Roll-in cohort: Reduction in tricuspid regurgitation (TR) grade by at least one grade
timeFrame: 1 year
measure: Roll-in cohort: Reduction in New York Heart Association (NYHA) functional class by at least one grade
timeFrame: 1 year
measure: Roll-in cohort: Change in Quality of Life (QOL) as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline
timeFrame: 1 year
measure: Roll-in cohort: Death and heart failure hospitalization
timeFrame: 1 year
measure: Roll-in cohort: All-cause hospitalizations
timeFrame: 1 year
measure: Roll-in cohort: All-cause mortality
timeFrame: 1 year
measure: Roll-in cohort: Change in 6MWD from baseline
timeFrame: 1 year
measure: Registry cohort: Tricuspid Regurgitation (TR) grade reduction
timeFrame: Time Frame: Discharge (assessed up to 7 days post procedure)
measure: Registry cohort: All-cause mortality
timeFrame: 1 year, annually through 5 years
measure: Registry cohort: Heart failure hospitalizations
timeFrame: 1 year, annually through 5 years
measure: Registry cohort: Change in 6MWD from baseline
timeFrame: 1 year
measure: Registry cohort: Non-elective tricuspid valve re-intervention (percutaneous or surgical)
timeFrame: 1 year, annually through 5 years
measure: Registry cohort: Durable RVAD implantation or heart transplant
timeFrame: 1 year, annually through 5 years
measure: Registry cohort: Need for paracentesis
timeFrame: 1 year, annually through 5 years
measure: Registry cohort: Reduction in TR grade by at least one grade
timeFrame: 1 year
measure: Registry cohort: Reduction in New York Heart Association (NYHA) functional class by at least one grade
timeFrame: 1 year
measure: Registry cohort: Change in Quality of Life (QOL) as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline
timeFrame: 1 year
measure: Registry cohort: Death and heart failure hospitalization
timeFrame: 1 year
measure: Registry cohort: All-cause hospitalizations
timeFrame: 1 year
measure: Registry cohort: All-cause mortality
timeFrame: 1 year
measure: Continued Access Study: Tricuspid Regurgitation (TR) grade reduction
timeFrame: Time Frame: Discharge (assessed up to 7 days post procedure)
measure: Continued Access Study: All-cause mortality
timeFrame: 1 year, annually through 5 years
measure: Continued Access Study: Heart failure hospitalizations
timeFrame: 1 year, annually through 5 years
measure: Continued Access Study: Non-elective tricuspid valve re-intervention (percutaneous or surgical)
timeFrame: 1 year, annually through 5 years
measure: Continued Access Study: Durable RVAD implantation or heart transplant
timeFrame: 1 year, annually through 5 years
measure: Continued Access Study: Need for paracentesis
timeFrame: 1 year, annually through 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: SJHMC Heart and Vascular Institute
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Memorial Hospital La Jolla
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Loveland
country: United States
facility: Medical Center of the Rockies
state: Colorado
city: Atlantis
country: United States
facility: Florida Heart & Vascular Care - JFK
state: Florida
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute Research Foundation
state: Florida
city: Naples
country: United States
facility: NCH Heart Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Heart Center of Indiana
state: Indiana
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi St. Francis
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital and Health Systems
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: State University of New York at Buffalo
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine-New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Columbia University Medical Center/NYPH
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Heart Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Saint Thomas Health
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: HCA Houston Healthcare
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Plano
country: United States
facility: Baylor Heart Hopsital Plano
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Franciscan Health
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW, Bad Oeynhausen
city: Bonn
country: Germany
facility: Herzzentrum Universitätsklinik Bonn
city: Dresden
country: Germany
facility: Herzzentrum Dresden Universitätsklinik
city: Köln
country: Germany
facility: Herzzentrum der Uniklinik Köln
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität Mainz
city: München
country: Germany
facility: Klinikum der Universität München - Großhadern
Study officials:
affiliation: Columbia University
name: Rebecca Hahn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Susheel Kodali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Herzzentrum Leipzig GmbH
name: Philipp Lurz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Piedmont Heart Institute
name: Vinod Thourani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kodali S, Hahn RT, George I, Davidson CJ, Narang A, Zahr F, Chadderdon S, Smith R, Grayburn PA, O'Neill WW, Wang DD, Herrmann H, Silvestry F, Elmariah S, Inglessis I, Passeri J, Lim DS, Salerno M, Makar M, Mack MJ, Leon MB, Makkar R; TRISCEND Investigators. Transfemoral Tricuspid Valve Replacement in Patients With Tricuspid Regurgitation: TRISCEND Study 30-Day Results. JACC Cardiovasc Interv. 2022 Mar 14;15(5):471-480. doi: 10.1016/j.jcin.2022.01.016.
citation: Lurz P, Kresoja KP. Tricuspid Valve Therapies: Closing the Gap. JACC Cardiovasc Interv. 2021 Jun 14;14(11):1241-1242. doi: 10.1016/j.jcin.2021.04.008. No abstract available.