Reducing Lung CongestIon Symptoms in Advanced Heart Failure (RELIEVE-HF)

RELIEVE-HF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure

The objective of the RELIEVE-HF study is to provide reasonable assurance of safety and effectiveness of the V-Wave Interatrial Shunt System by improving meaningful clinical outcomes in patients with New York Heart Association (NYHA) functional Class II, Class III, or ambulatory Class IV heart failure (HF), irrespective of left ventricular ejection fraction, who at baseline are treated with guideline-directed drug and device therapies.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: V-Wave Interatrial Shunt; Other: Control

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 605
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• 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

Main 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.
Other: 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; Right heart catheterization, invasive echocardiography.
Experimental: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety-Percentage of Treatment patients experiencing major device-related adverse events	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	30-days after randomization
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)	Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method	Follow-up duration at endpoint analysis ranges from a minimum of 12 to a maximum of 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6MWT changes	6MWT changes	Baseline to 12 months
KCCQ changes	KCCQ changes	Baseline to 12 months
KCCQ changes	KCCQ changes	Baseline through study completion, maximum of five years
Time to all-cause death, LVAD/Transplant, or heart failure hospitalization	Time to all-cause death, LVAD/Transplant, or heart failure hospitalization	Baseline through study completion, maximum of five years
Time to all-cause death or first heart failure hospitalization	Time to all-cause death or first heart failure hospitalization	Baseline through study completion, maximum of five years
Cumulative heart failure hospitalizations	Cumulative heart failure hospitalizations	Baseline through study completion, maximum of five years
Time to first heart failure hospitalization	Time to first heart failure hospitalization	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	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

Collaborators and Investigators

• Sponsor: V-Wave Ltd
• 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

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2018
• Primary Completion (Actual): October 9, 2023
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (Actual): April 17, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 18, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: CL7018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes