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Heart FailureRELIEVE-HFNCT03499236

Reducing Lung CongestIon Symptoms in Advanced Heart Failure

A study testing V-Wave Interatrial Shunt in people with Heart Failure, run by V-Wave Ltd at 83 sites in 11 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Heart Failure
What is being tested?
V-Wave Interatrial Shunt
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
605 participants
Where
83 sitesin 11 countries
Study dates
19 Sep 2018to 31 Oct 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

83 sites in 11 countries.

83 sites in 11 countries

United States43 sites

  • Summa Health

    Akron, Ohio, 44304

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Austin Heart

    Austin, Texas, 78756

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Lindner Center for Research and Education at The Christ Hospital

    Cincinnati, Ohio, 45219

  • Cleveland Clinic

    Cleveland, Ohio, 80120

  • The Ohio State University

    Columbus, Ohio, 43210

  • St Elizabeth Medical Center

    Edgewood, Kentucky, 41017

  • Northeast Georgia Medical Center

    Gainesville, Georgia, 30501

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Texas Heart Institute

    Houston, Texas, 77030

  • University of Texas Memorial Hermann

    Houston, Texas, 77030

  • Memorial Hospital

    Jacksonville, Florida, 32216

  • Scripps Health

    La Jolla, California, 92037

  • Nebraska Heart Institute

    Lincoln, Nebraska, 68526

  • South Denver Cardiology

    Littleton, Colorado, 80120

  • Long Beach Memorial Medical Center

    Long Beach, California, 90806

  • Keck Medical Center of USC

    Los Angeles, California, 90033

  • Cedars Sinai Medical Center

    Los Angeles, California, 90211

  • University of Miami

    Miami, Florida, 33136

  • Midwest Cardiovascular Institute

    Naperville, Illinois, 60540

  • Centennial Medical Center

    Nashville, Tennessee, 37203

  • Weill Cornell

    New York, New York, 10065

  • First Coast Cardiovascular Institute

    Orange Park, Florida, 32003

  • Abrazo Arizona Heart Hospital

    Phoenix, Arizona, 85016

  • Arizona Heart Rhythm Center

    Phoenix, Arizona, 85016

  • North Carolina Heart & Vascular

    Raleigh, North Carolina, 27607

  • Chippenham Medical Center

    Richmond, Virginia, 23225

  • Valley Health System

    Ridgewood, New Jersey, 07450

  • Rochester General Health System

    Rochester, New York, 14621

  • United Heart & Vascular Clinic

    Saint Paul, Minnesota, 55102

  • University of Utah Hospital

    Salt Lake City, Utah, 84132

  • Methodist Hospital

    San Antonio, Texas, 78249

  • Kaiser Permanente San Francisco

    San Francisco, California, 94118

  • University of California, San Francisco

    San Francisco, California, 94143

  • Stanford Hospital

    Stanford, California, 94305

  • Los Robles Hospital & Medical Center

    Thousand Oaks, California, 91360

  • The Lundquist Institute (Harbor-UCLA) Medical Center

    Torrance, California, 90502

  • Christus Mother Frances Hospital

    Tyler, Texas, 75701

  • UPMC Pinnacle / Pinnacle Health Cardiovascular Institute

    Wormleysburg, Pennsylvania, 17043

Other trials in United States

Germany9 sites

  • Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum

    Berlin, 10117

  • Vivantes Klinikum im Friedrichshain

    Berlin, 10249

  • Vivantes Klinikum Urban

    Berlin

  • Marienkrankrankenhas

    Hamburg

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Herzzentrum Leipzig

    Leipzig, 04289

  • Ludwig-Maximilians-Universität München

    München, 81377

  • SANA Remscheid

    Remscheid

  • University of Rostock

    Rostock

Other trials in Germany

Israel7 sites

  • University Hospital Samson Assuta Ashdod

    Ashdod, 7747629

  • Yitzhak Shamir Medical Center

    Be’er Ya‘aqov

  • Hadassah Medical Center

    Jerusalem

  • The Chaim Sheba Medical Center Tel-Hashomer

    Ramat Gan, 52621

  • Kaplan Medical Center

    Rehovot

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

  • The Baruch Padeh Medical Center, Poriya

    Tiberias, 15208

Other trials in Israel

Spain7 sites

  • Hospital Clinic of Barcelona

    Barcelona, 08036

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, 08041

  • Hospital Universitari Germans Trias i Pujol, Badalona Barcelona

    Barcelona, 08916

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Puerta de Hierro-Majadahonda

    Madrid, 28222

  • Hospital Clínico Universitario de Valencia

    Valencia, 46010

  • Hospital Clínico Universitario de Valladolid

    Valladolid, 47003

Other trials in Spain

Australia4 sites

  • Flinders Medical Centre

    Adelaide

  • Prince Charles Hospital

    Brisbane

  • St. Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • St. Vincent's Hospital

    Melbourne

Other trials in Australia

Netherlands3 sites

  • Academic Medical Center, The Netherlands

    Amsterdam, 1105

  • St Antonius Ziekenhuis Nieuwegein

    Nieuwegein, Utrecht, 3435

  • Erasmus University Medical Center Rotterdam

    Rotterdam, 3015

Other trials in Netherlands

Poland3 sites

  • Institute of Cardiology, Warsaw

    Warsaw

  • The 4th Military Clinical Hospital Wroclaw

    Wroclaw

  • University Hospital Wroclaw

    Wroclaw

Other trials in Poland

Belgium2 sites

  • Ziekenhuis Aan De Stroom vzw (ZAS)

    Antwerp

  • AZ Sint-Jan Brugge

    Bruges

Other trials in Belgium

Canada2 sites

  • Montréal Heart Institute

    Montreal

  • Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

    Québec, G1V 4G5

Other trials in Canada

Switzerland2 sites

  • Bern University Hospital

    Bern, 3010

  • University Hospital of Zürich

    Zurich, 8091

Other trials in Switzerland

New Zealand1 site

  • Christchurch Hospital

    Christchurch

Other trials in New Zealand

About this study

Official title: 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.

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.

Conditions
Heart Failure
Being tested
V-Wave Interatrial Shunt, Control
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • V-Wave Interatrial ShuntDevice

    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.

  • ControlOther

    Right heart catheterization, invasive echocardiography.

Study groups in NCT03499236
Study groupRoleWhat they receive
TreatmentExperimentalTreatment 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
Receives: Device: V-Wave Interatrial Shunt
ControlOtherControl 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.
Receives: Other: Control
Roll inExperimentalRoll 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
Receives: Device: V-Wave Interatrial Shunt

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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

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

Secondary outcomes (8)

  1. 6MWT changes

    6MWT changes

    Measured: Baseline to 12 months

  2. KCCQ changes

    KCCQ changes

    Measured: Baseline to 12 months

  3. KCCQ changes

    KCCQ changes

    Measured: 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

    Measured: 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

    Measured: Baseline through study completion, maximum of five years

  6. Cumulative heart failure hospitalizations

    Cumulative heart failure hospitalizations

    Measured: Baseline through study completion, maximum of five years

  7. Time to first heart failure hospitalization

    Time to first heart failure hospitalization

    Measured: 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

    Measured: Baseline through study completion, maximum of five years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2018
  2. Study start19 Sep 2018
  3. Primary completion9 Oct 2023
  4. Study completion31 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized treatment versus control (1:1). Control patients will be allowed to cross-over at the completion of the blinded phase. A parallel roll-in arm will enroll up to 2 patients per site in an open-label study.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
605 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03499236
Sponsor's protocol ID
CL7018
Acronym
RELIEVE-HF
Status last verified
Nov 2024
First submitted
29 Mar 2018
Last updated
19 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes

Publications

  • Rodes-Cabau J, Stone GW, Kar S, Verheye S, Roguin A, Bax J, Bayes-Genis A, Nunez J, Depta J, Laufer-Perl M, Moravsky G, Romero A, Prihadi E, Chung ES, Price MJ, Chenier M, Schewel D, Kumar S, Kische S, Bhatt K, Shah KS, Donovan DJ, Hendrix S, O'Keefe P, Abraham WT, Zile MR, Anker SD, Eigler NL, Lindenfeld J; RELIEVE-HF Investigators. Long-Term Safety and Procedural Performance of an Interatrial Shunt for Heart Failure According to Ejection Fraction. JACC Heart Fail. 2026 Oct 13:103375. doi: 10.1016/j.jchf.2026.103375. Online ahead of print.

    PubMed 42886087

  • Stone GW, Lindenfeld J, Zile MR, Anker SD, Rodes-Cabau J, Snyder C, Kar S, Pfeiffer MP, Bayes-Genis A, Bax JJ, Bank AJ, Nunez J, Lee EC, Laufer-Perl M, Moravsky G, Litwin SE, Holcomb R, Eigler NL, Abraham WT; RELIEVE-HF Investigators. Modeling Individual Patient Outcomes After Interatrial Shunt Treatment in Heart Failure With Reduced and Preserved Ejection Fraction: The RELIEVE-HF Trial. Circ Heart Fail. 2026 Aug 4:e014100. doi: 10.1161/CIRCHEARTFAILURE.125.014100. Online ahead of print.

    PubMed 42550570

  • 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

Questions about this trial

What is this clinical trial studying?

A study testing V-Wave Interatrial Shunt in people with Heart Failure, run by V-Wave Ltd at 83 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 83 sites in United States, Germany, Israel, Spain, Australia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety-Percentage of Treatment patients experiencing major device-related adverse events (time frame: 30-days after randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03499236, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2025.

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