Study Description

This is a prospective, multi-center, 1:1 randomized, patient and observer blinded clinical study, with a Shunt Treatment arm and a non-implant Control arm. A total of approximately 500 patients will be randomized. Patients and all research staff managing the patients after randomization will be blinded during follow-up for a minimum of 12 months to a maximum of 24 months. Control patients will have the opportunity to receive a shunt after 24 months once unblinding occurs, if they provide consent, and continue to meet inclusion/exclusion criteria. All implanted patients will be followed for a total of 5 years from the time of the study device implantation.

Condition or Disease	Intervention/Treatment
Heart Failure	Device: V-Wave Interatrial Shunt Other: Control

Study Design

Study Type	Interventional
Actual Enrollment	605 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	RELIEVE-HF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure
Study Start Date	September 19, 2018
Actual Primary Completion Date	October 9, 2023
Anticipated Study Completion Date	October 31, 2027

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Treatment Treatment arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by transseptal catheterization and V-Wave Shunt implantation	Device: V-Wave Interatrial Shunt The V-Wave Interatrial Shunt System, includes a permanent implant placed during a minimally invasive cardiac catheterization procedure using its dedicated Delivery Catheter. The device is implanted through the fossa ovalis and straddles the interatrial septum.
Control Control arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility, but will not have transseptal catheterization or shunt implantation.	Other: Control
Roll in Roll in arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by transseptal catheterization and V-Wave Shunt implantation	Device: V-Wave Interatrial Shunt The V-Wave Interatrial Shunt System, includes a permanent implant placed during a minimally invasive cardiac catheterization procedure using its dedicated Delivery Catheter. The device is implanted through the fossa ovalis and straddles the interatrial septum.

Outcome Measures

Primary Outcome Measures

1. Safety-Percentage of Treatment patients experiencing major device-related adverse events [30-days after randomization]
   Percentage of Treatment group patients experiencing any device-related Major Adverse Cardiovascular or Neurological Events (MACNE) during the first 30-days after randomization, compared to a pre-specified Performance Goal
2. Effectiveness-Hierarchical composite of death, heart transplant or left ventricular assist device (LVAD) implantation, HF hospitalizations, worsening HF events treated as an outpatient, and change in Kansas City Cardiomyopathy Questionnaire (KCCQ) [Follow-up duration at endpoint analysis ranges from a minimum of 12 to a maximum of 24 months]
   Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method

Secondary Outcome Measures

1. 6MWT changes [Baseline to 12 months]
   6MWT changes
2. KCCQ changes [Baseline to 12 months]
   KCCQ changes
3. KCCQ changes [Baseline through study completion, maximum of five years]
   KCCQ changes
4. Time to all-cause death, LVAD/Transplant, or heart failure hospitalization [Baseline through study completion, maximum of five years]
   Time to all-cause death, LVAD/Transplant, or heart failure hospitalization
5. Time to all-cause death or first heart failure hospitalization [Baseline through study completion, maximum of five years]
   Time to all-cause death or first heart failure hospitalization
6. Cumulative heart failure hospitalizations [Baseline through study completion, maximum of five years]
   Cumulative heart failure hospitalizations
7. Time to first heart failure hospitalization [Baseline through study completion, maximum of five years]
   Time to first heart failure hospitalization
8. Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ [Baseline through study completion, maximum of five years]
   Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ

Eligibility Criteria

Ages Eligible for Study	18 Years to 99 Years (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	No
Inclusion Criteria	ia: Both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) patients NYHA Class II, Class III, or ambulatory Class IV HF Receiving guideline directed medical and device therapy (GDMT) for heart failure For NYHA Class III and ambulatory Class IV, at least one prior hospitalization for heart failure within the last year or elevated BNP level of at least 300 pg/ml or NT-proBNP level of at least 1,500 pg/ml. BNP/NT-ProBNP levels corrected for BMI For NYHA Class II, must have both hospitalization and elevated BNP levels as above specifications Mai
Exclusion Criteria	Systolic blood pressure <90 or >160 mmHg Presence of Intracardiac thrombus Pulmonary hypertension with PASP of ≥70 mm/Hg or PVR > 4 WU Significant RV dysfunction - TAPSE <12mm or RVFAC ≤25% Left Ventricular End-Diastolic Diameter (LVEDD) >8cm Moderate to severe aortic or mitral stenosis Stroke or TIA or DVT within the last 6 months eGFR <25 ml/min/1.73 m^2 Anatomical anomaly on TEE or ICE that precludes implantation of Shunt across fossa ovalis (FO) of the interatrial septum Inadequate vascular access for implantation of shunt, e.g. femoral venous access for transseptal catheterization and inferior vena cava (IVC) is not patent Hemodynamic heart rhythm, or respiratory instability at time of Final Exclusion Criteria

Contacts and Locations

Sponsors and Collaborators	V-Wave Ltd
Locations	Abrazo Arizona Heart Hospital | Phoenix, Arizona, United States, 85016 Arizona Heart Rhythm Center | Phoenix, Arizona, United States, 85016 Scripps Health | La Jolla, California, United States, 92037 Long Beach Memorial Medical Center | Long Beach, California, United States, 90806 Keck Medical Center of USC | Los Angeles, California, United States, 90033 Cedars Sinai Medical Center | Los Angeles, California, United States, 90211 Kaiser Permanente San Francisco | San Francisco, California, United States, 94118 University of California, San Francisco | San Francisco, California, United States, 94143 Stanford Hospital | Stanford, California, United States, 94305 Los Robles Hospital & Medical Center | Thousand Oaks, California, United States, 91360 The Lundquist Institute (Harbor-UCLA) Medical Center | Torrance, California, United States, 90502 South Denver Cardiology | Littleton, Colorado, United States, 80120 Memorial Hospital | Jacksonville, Florida, United States, 32216 University of Miami | Miami, Florida, United States, 33136 First Coast Cardiovascular Institute | Orange Park, Florida, United States, 32003 Piedmont Hospital | Atlanta, Georgia, United States, 30309 Northeast Georgia Medical Center | Gainesville, Georgia, United States, 30501 Rush University Medical Center | Chicago, Illinois, United States, 60612 Midwest Cardiovascular Institute | Naperville, Illinois, United States, 60540 St Elizabeth Medical Center | Edgewood, Kentucky, United States, 41017 United Heart & Vascular Clinic | Saint Paul, Minnesota, United States, 55102 Nebraska Heart Institute | Lincoln, Nebraska, United States, 68526 Valley Health System | Ridgewood, New Jersey, United States, 07450 Weill Cornell | New York, New York, United States, 10065 Northwell Health Lenox Hill Hospital | New York, New York, United States, 10075 Rochester General Health System | Rochester, New York, United States, 14621 Mission Hospital | Asheville, North Carolina, United States, 28801 North Carolina Heart & Vascular | Raleigh, North Carolina, United States, 27607 Summa Health | Akron, Ohio, United States, 44304 Lindner Center for Research and Education at The Christ Hospital | Cincinnati, Ohio, United States, 45219 Cleveland Clinic | Cleveland, Ohio, United States, 80120 The Ohio State University | Columbus, Ohio, United States, 43210 Penn State Milton S. Hershey Medical Center | Hershey, Pennsylvania, United States, 17033 UPMC Pinnacle / Pinnacle Health Cardiovascular Institute | Wormleysburg, Pennsylvania, United States, 17043 Medical University of South Carolina | Charleston, South Carolina, United States, 29425 Centennial Medical Center | Nashville, Tennessee, United States, 37203 Austin Heart | Austin, Texas, United States, 78756 Baylor College of Medicine | Houston, Texas, United States, 77030 Texas Heart Institute | Houston, Texas, United States, 77030 University of Texas Memorial Hermann | Houston, Texas, United States, 77030 Methodist Hospital | San Antonio, Texas, United States, 78249 Christus Mother Frances Hospital | Tyler, Texas, United States, 75701 University of Utah Hospital | Salt Lake City, Utah, United States, 84132 Chippenham Medical Center | Richmond, Virginia, United States, 23225 St. Vincent's Hospital Sydney | Darlinghurst, New South Wales, Australia, 2010 Flinders Medical Centre | Adelaide, Australia, Prince Charles Hospital | Brisbane, Australia, St. Vincent's Hospital | Melbourne, Australia, Epworth Hospital | Richmond, Australia, Ziekenhuis Aan De Stroom vzw (ZAS) | Antwerp, Belgium, AZ Sint-Jan Brugge | Brugge, Belgium, Montréal Heart Institute | Montréal, Canada, Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval | Québec, Canada, G1V 4G5 Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum | Berlin, Germany, 10117 Vivantes Klinikum im Friedrichshain | Berlin, Germany, 10249 Vivantes Klinikum Urban | Berlin, Germany, Marienkrankrankenhas | Hamburg, Germany, Universitätsklinikum Leipzig | Leipzig, Germany, 04103 Herzzentrum Leipzig | Leipzig, Germany, 04289 Universitatsmedizin Mainz | Mainz, Germany, 55131 Ludwig-Maximilians-Universität München | München, Germany, 81377 SANA Remscheid | Remscheid, Germany, University of Rostock | Rostock, Germany, University Hospital Samson Assuta Ashdod | Ashdod, Israel, 7747629 Yitzhak Shamir Medical Center | Be'er Ya'aqov, Israel, Soroka University Medical Center | Beer-Sheva, Israel, 84101 Rambam Medical Center | Haifa, Israel, 31906 Shaare Zedek Medical Center | Jerusalem, Israel, 9103102 Hadassah Medical Center | Jerusalem, Israel, The Chaim Sheba Medical Center Tel-Hashomer | Ramat Gan, Israel, 52621 Kaplan Medical Center | Rechovot, Israel, Tel Aviv Sourasky Medical Center | Tel Aviv, Israel, The Baruch Padeh Medical Center, Poriya | Tiberias, Israel, 15208 St Antonius Ziekenhuis Nieuwegein | Nieuwegein, Utrecht, Netherlands, 3435 Academic Medical Center, The Netherlands | Amsterdam, Netherlands, 1105 Erasmus University Medical Center Rotterdam | Rotterdam, Netherlands, 3015 Christchurch Hospital | Christchurch, New Zealand, Auckland Hospital | Grafton, New Zealand, 1142 Górnośląskie Centrum Medyczne, Uniwersytetu Medycznego w Katowicach | Katowice, Poland, 40-635 Institute of Cardiology, Warsaw | Warszawa, Poland, The 4th Military Clinical Hospital Wroclaw | Wrocław, Poland, University Hospital Wroclaw | Wrocław, Poland, Hospital Clinic of Barcelona | Barcelona, Spain, 08036 Hospital de la Santa Creu i Sant Pau | Barcelona, Spain, 08041 Hospital Universitari Germans Trias i Pujol, Badalona Barcelona | Barcelona, Spain, 08916 Hospital Clínico San Carlos | Madrid, Spain, 28040 Hospital Puerta de Hierro-Majadahonda | Madrid, Spain, 28222 University Hospital Virgen de la Arrixaca | Murcia, Spain, 30120 Hospital Clínico Universitario de Valencia | Valencia, Spain, 46010 Hospital Clínico Universitario de Valladolid | Valladolid, Spain, 47003 Bern University Hospital | Bern, Switzerland, 3010 University Hospital of Zürich | Zürich, Switzerland, 8091
Investigators	Principal Investigator: Stefan D Anker, MD, PhD, University Medical Center Gottingen, Germany Principal Investigator: JoAnn Lindenfeld, MD, Vanderbilt University Principal Investigator: Josep Rodés-Cabau, MD, Université Laval (CRIUCPQ-ULaval) Principal Investigator: Gregg W Stone, MD, Colombia University Medical Center

More Information

Additional Relevant MeSH Terms

• Heart Failure
• Heart Diseases
• Cardiovascular Diseases