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Active, not recruitingNCT03499236RELIEVE-HFUpdated Aug 19, 2025

Reducing Lung CongestIon Symptoms in Advanced Heart Failure

An interventional study of V-Wave Interatrial Shunt and Control in Heart Failure, sponsored by V-Wave Ltd. Active, not recruiting at 83 sites in 11 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2025-08-19.

Sponsored by V-Wave Ltd · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
605
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Heart Failure

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03

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
605 participants (actual)

Study arms

  • 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

  • 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

  • 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

Interventions

  • DeviceV-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.

  • OtherControl

    Right heart catheterization, invasive echocardiography.

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: 30-days after randomization

  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)

    Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method

    Time frame: Follow-up duration at endpoint analysis ranges from a minimum of 12 to a maximum of 24 months

Secondary outcomes

  1. 6MWT changes

    6MWT changes

    Time frame: Baseline to 12 months

  2. KCCQ changes

    KCCQ changes

    Time frame: Baseline to 12 months

  3. KCCQ changes

    KCCQ changes

    Time frame: Baseline through study completion, maximum of five years

  4. Time to all-cause death, LVAD/Transplant, or heart failure hospitalization

    Time to all-cause death, LVAD/Transplant, or heart failure hospitalization

    Time frame: Baseline through study completion, maximum of five years

  5. Time to all-cause death or first heart failure hospitalization

    Time to all-cause death or first heart failure hospitalization

    Time frame: Baseline through study completion, maximum of five years

  6. Cumulative heart failure hospitalizations

    Cumulative heart failure hospitalizations

    Time frame: Baseline through study completion, maximum of five years

  7. Time to first heart failure hospitalization

    Time to first heart failure hospitalization

    Time frame: Baseline through study completion, maximum of five years

  8. 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

    Time frame: Baseline through study completion, maximum of five years

06

Study locations

83 sites
  • Abrazo Arizona Heart Hospital
    Phoenix, Arizona 85016, United States
  • Arizona Heart Rhythm Center
    Phoenix, Arizona 85016, United States
  • Scripps Health
    La Jolla, California 92037, United States
  • Long Beach Memorial Medical Center
    Long Beach, California 90806, United States
  • Keck Medical Center of USC
    Los Angeles, California 90033, United States
  • Cedars Sinai Medical Center
    Los Angeles, California 90211, United States
  • Kaiser Permanente San Francisco
    San Francisco, California 94118, United States
  • University of California, San Francisco
    San Francisco, California 94143, United States
  • Stanford Hospital
    Stanford, California 94305, United States
  • Los Robles Hospital & Medical Center
    Thousand Oaks, California 91360, United States
  • The Lundquist Institute (Harbor-UCLA) Medical Center
    Torrance, California 90502, United States
  • South Denver Cardiology
    Littleton, Colorado 80120, United States
  • Memorial Hospital
    Jacksonville, Florida 32216, United States
  • University of Miami
    Miami, Florida 33136, United States
  • First Coast Cardiovascular Institute
    Orange Park, Florida 32003, United States
  • Piedmont Hospital
    Atlanta, Georgia 30309, United States
  • Northeast Georgia Medical Center
    Gainesville, Georgia 30501, United States
  • Rush University Medical Center
    Chicago, Illinois 60612, United States
  • Midwest Cardiovascular Institute
    Naperville, Illinois 60540, United States
  • St Elizabeth Medical Center
    Edgewood, Kentucky 41017, United States
  • United Heart & Vascular Clinic
    Saint Paul, Minnesota 55102, United States
  • Nebraska Heart Institute
    Lincoln, Nebraska 68526, United States
  • Valley Health System
    Ridgewood, New Jersey 07450, United States
  • Weill Cornell
    New York, New York 10065, United States
  • Rochester General Health System
    Rochester, New York 14621, United States
  • Mission Hospital
    Asheville, North Carolina 28801, United States
  • North Carolina Heart & Vascular
    Raleigh, North Carolina 27607, United States
  • Summa Health
    Akron, Ohio 44304, United States
  • Lindner Center for Research and Education at The Christ Hospital
    Cincinnati, Ohio 45219, United States
  • Cleveland Clinic
    Cleveland, Ohio 80120, United States
  • The Ohio State University
    Columbus, Ohio 43210, United States
  • Penn State Milton S. Hershey Medical Center
    Hershey, Pennsylvania 17033, United States
  • UPMC Pinnacle / Pinnacle Health Cardiovascular Institute
    Wormleysburg, Pennsylvania 17043, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • Centennial Medical Center
    Nashville, Tennessee 37203, United States
  • Austin Heart
    Austin, Texas 78756, United States
  • Baylor College of Medicine
    Houston, Texas 77030, United States
  • Texas Heart Institute
    Houston, Texas 77030, United States
  • University of Texas Memorial Hermann
    Houston, Texas 77030, United States
  • Methodist Hospital
    San Antonio, Texas 78249, United States
  • Christus Mother Frances Hospital
    Tyler, Texas 75701, United States
  • University of Utah Hospital
    Salt Lake City, Utah 84132, United States
  • Chippenham Medical Center
    Richmond, Virginia 23225, United States
  • St. Vincent's Hospital Sydney
    Darlinghurst, New South Wales 2010, Australia
  • Flinders Medical Centre
    Adelaide, Australia
  • Prince Charles Hospital
    Brisbane, Australia
  • St. Vincent's Hospital
    Melbourne, Australia
  • Ziekenhuis Aan De Stroom vzw (ZAS)
    Antwerp, Belgium
  • AZ Sint-Jan Brugge
    Bruges, Belgium
  • Montréal Heart Institute
    Montreal, Canada
  • Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
    Québec, G1V 4G5, Canada
  • Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum
    Berlin, 10117, Germany
  • Vivantes Klinikum im Friedrichshain
    Berlin, 10249, Germany
  • Vivantes Klinikum Urban
    Berlin, Germany
  • Marienkrankrankenhas
    Hamburg, Germany
  • Universitätsklinikum Leipzig
    Leipzig, 04103, Germany
  • Herzzentrum Leipzig
    Leipzig, 04289, Germany
  • Ludwig-Maximilians-Universität München
    München, 81377, Germany
  • SANA Remscheid
    Remscheid, Germany
  • University of Rostock
    Rostock, Germany
  • University Hospital Samson Assuta Ashdod
    Ashdod, 7747629, Israel
  • Yitzhak Shamir Medical Center
    Be’er Ya‘aqov, Israel
  • Hadassah Medical Center
    Jerusalem, Israel
  • The Chaim Sheba Medical Center Tel-Hashomer
    Ramat Gan, 52621, Israel
  • Kaplan Medical Center
    Rehovot, Israel
  • Tel Aviv Sourasky Medical Center
    Tel Aviv, Israel
  • The Baruch Padeh Medical Center, Poriya
    Tiberias, 15208, Israel
  • St Antonius Ziekenhuis Nieuwegein
    Nieuwegein, Utrecht 3435, Netherlands
  • Academic Medical Center, The Netherlands
    Amsterdam, 1105, Netherlands
  • Erasmus University Medical Center Rotterdam
    Rotterdam, 3015, Netherlands
  • Christchurch Hospital
    Christchurch, New Zealand
  • Institute of Cardiology, Warsaw
    Warsaw, Poland
  • The 4th Military Clinical Hospital Wroclaw
    Wroclaw, Poland
  • University Hospital Wroclaw
    Wroclaw, Poland
  • Hospital Clinic of Barcelona
    Barcelona, 08036, Spain
  • Hospital de la Santa Creu i Sant Pau
    Barcelona, 08041, Spain
  • Hospital Universitari Germans Trias i Pujol, Badalona Barcelona
    Barcelona, 08916, Spain
  • Hospital Clínico San Carlos
    Madrid, 28040, Spain
  • Hospital Puerta de Hierro-Majadahonda
    Madrid, 28222, Spain
  • Hospital Clínico Universitario de Valencia
    Valencia, 46010, Spain
  • Hospital Clínico Universitario de Valladolid
    Valladolid, 47003, Spain
  • Bern University Hospital
    Bern, 3010, Switzerland
  • University Hospital of Zürich
    Zurich, 8091, Switzerland
07

References and documents

Publications

  • Zile MR, Abraham WT, Lindenfeld J, Anker SD, Rodes-Cabau J, Pfeiffer MP, Boehmer JP, Litwin S, Baicu CF, Villota JN, Lee EC, Holcomb R, O'Keefe P, Eigler NL, Stone GW; RELIEVE-HF Investigators. Mechanistic Basis for Differential Effects of Interatrial Shunt Treatment in HFrEF vs HFpEF: The RELIEVE-HF Trial. JACC Cardiovasc Imaging. 2026 Jan;19(1):1-15. doi: 10.1016/j.jcmg.2025.08.005. Epub 2025 Sep 15. PubMed 40892630 ↗
  • Stone GW, Lindenfeld J, Rodes-Cabau J, Anker SD, Zile MR, Kar S, Holcomb R, Pfeiffer MP, Bayes-Genis A, Bax JJ, Bank AJ, Costanzo MR, Verheye S, Roguin A, Filippatos G, Nunez J, Lee EC, Laufer-Perl M, Moravsky G, Litwin SE, Prihadi E, Gada H, Chung ES, Price MJ, Thohan V, Schewel D, Kumar S, Kische S, Shah KS, Donovan DJ, Zhang Y, Eigler NL, Abraham WT; RELIEVE-HF Investigators. Interatrial Shunt Treatment for Heart Failure: The Randomized RELIEVE-HF Trial. Circulation. 2024 Dec 10;150(24):1931-1943. doi: 10.1161/CIRCULATIONAHA.124.070870. Epub 2024 Sep 23. PubMed 39308371 ↗

Individual participant data

Plan to share: Yes

08

Registry details

Key details

Study ID
NCT03499236
Lead sponsor
V-Wave Ltd
Responsible party
Sponsor
First posted
Apr 17, 2018
Start date
Sep 19, 2018
Primary completion
Oct 9, 2023
Completion
Oct 31, 2027 (estimated)
Last update
Aug 19, 2025

Study contacts

Stefan D Anker, MD, PhD
principal investigator · University Medical Center Gottingen, Germany
JoAnn Lindenfeld, MD
principal investigator · Vanderbilt University
Josep Rodés-Cabau, MD
principal investigator · Université Laval (CRIUCPQ-ULaval)
Gregg W Stone, MD
principal investigator · Colombia University Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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