Reducing Lung CongestIon Symptoms in Advanced Heart Failure

NCT ID: NCT03499236

Last Updated: 2025-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

605 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-19

Study Completion Date

2027-10-31

Brief Summary

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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.

Detailed Description

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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

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
In the randomized cohort, participants, the clinical team, and research staff managing the patient after randomization will be blinded to study assignment.

Study Groups

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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

Group Type EXPERIMENTAL

V-Wave Interatrial Shunt

Intervention Type DEVICE

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.

Group Type OTHER

Control

Intervention Type OTHER

Right heart catheterization, invasive echocardiography.

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

Group Type EXPERIMENTAL

V-Wave Interatrial Shunt

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

Control

Right heart catheterization, invasive echocardiography.

Intervention Type OTHER

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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V-Wave Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stefan D Anker, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Gottingen, Germany

JoAnn Lindenfeld, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Josep Rodés-Cabau, MD

Role: PRINCIPAL_INVESTIGATOR

Université Laval (CRIUCPQ-ULaval)

Gregg W Stone, MD

Role: PRINCIPAL_INVESTIGATOR

Colombia University Medical Center

Locations

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Abrazo Arizona Heart Hospital

Phoenix, Arizona, United States

Site Status

Arizona Heart Rhythm Center

Phoenix, Arizona, United States

Site Status

Scripps Health

La Jolla, California, United States

Site Status

Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

Keck Medical Center of USC

Los Angeles, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Kaiser Permanente San Francisco

San Francisco, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Stanford Hospital

Stanford, California, United States

Site Status

Los Robles Hospital & Medical Center

Thousand Oaks, California, United States

Site Status

The Lundquist Institute (Harbor-UCLA) Medical Center

Torrance, California, United States

Site Status

South Denver Cardiology

Littleton, Colorado, United States

Site Status

Memorial Hospital

Jacksonville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

First Coast Cardiovascular Institute

Orange Park, Florida, United States

Site Status

Piedmont Hospital

Atlanta, Georgia, United States

Site Status

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Midwest Cardiovascular Institute

Naperville, Illinois, United States

Site Status

St Elizabeth Medical Center

Edgewood, Kentucky, United States

Site Status

United Heart & Vascular Clinic

Saint Paul, Minnesota, United States

Site Status

Nebraska Heart Institute

Lincoln, Nebraska, United States

Site Status

Valley Health System

Ridgewood, New Jersey, United States

Site Status

Weill Cornell

New York, New York, United States

Site Status

Rochester General Health System

Rochester, New York, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

North Carolina Heart & Vascular

Raleigh, North Carolina, United States

Site Status

Summa Health

Akron, Ohio, United States

Site Status

Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

UPMC Pinnacle / Pinnacle Health Cardiovascular Institute

Wormleysburg, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Centennial Medical Center

Nashville, Tennessee, United States

Site Status

Austin Heart

Austin, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Texas Heart Institute

Houston, Texas, United States

Site Status

University of Texas Memorial Hermann

Houston, Texas, United States

Site Status

Methodist Hospital

San Antonio, Texas, United States

Site Status

Christus Mother Frances Hospital

Tyler, Texas, United States

Site Status

University of Utah Hospital

Salt Lake City, Utah, United States

Site Status

Chippenham Medical Center

Richmond, Virginia, United States

Site Status

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

Flinders Medical Centre

Adelaide, , Australia

Site Status

Prince Charles Hospital

Brisbane, , Australia

Site Status

St. Vincent's Hospital

Melbourne, , Australia

Site Status

Ziekenhuis Aan De Stroom vzw (ZAS)

Antwerp, , Belgium

Site Status

AZ Sint-Jan Brugge

Bruges, , Belgium

Site Status

Montréal Heart Institute

Montreal, , Canada

Site Status

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

Québec, , Canada

Site Status

Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Site Status

Vivantes Klinikum Urban

Berlin, , Germany

Site Status

Marienkrankrankenhas

Hamburg, , Germany

Site Status

Universitätsklinikum Leipzig

Leipzig, , Germany

Site Status

Herzzentrum Leipzig

Leipzig, , Germany

Site Status

Ludwig-Maximilians-Universität München

München, , Germany

Site Status

SANA Remscheid

Remscheid, , Germany

Site Status

University of Rostock

Rostock, , Germany

Site Status

University Hospital Samson Assuta Ashdod

Ashdod, , Israel

Site Status

Yitzhak Shamir Medical Center

Be’er Ya‘aqov, , Israel

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

The Chaim Sheba Medical Center Tel-Hashomer

Ramat Gan, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

The Baruch Padeh Medical Center, Poriya

Tiberias, , Israel

Site Status

St Antonius Ziekenhuis Nieuwegein

Nieuwegein, Utrecht, Netherlands

Site Status

Academic Medical Center, The Netherlands

Amsterdam, , Netherlands

Site Status

Erasmus University Medical Center Rotterdam

Rotterdam, , Netherlands

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Institute of Cardiology, Warsaw

Warsaw, , Poland

Site Status

The 4th Military Clinical Hospital Wroclaw

Wroclaw, , Poland

Site Status

University Hospital Wroclaw

Wroclaw, , Poland

Site Status

Hospital Clinic of Barcelona

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitari Germans Trias i Pujol, Badalona Barcelona

Barcelona, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Puerta de Hierro-Majadahonda

Madrid, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Clínico Universitario de Valladolid

Valladolid, , Spain

Site Status

Bern University Hospital

Bern, , Switzerland

Site Status

University Hospital of Zürich

Zurich, , Switzerland

Site Status

Countries

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United States Australia Belgium Canada Germany Israel Netherlands New Zealand Poland Spain Switzerland

References

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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. 2025 Sep 15:S1936-878X(25)00467-X. doi: 10.1016/j.jcmg.2025.08.005. Online ahead of print.

Reference Type DERIVED
PMID: 40892630 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39308371 (View on PubMed)

Other Identifiers

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CL7018

Identifier Type: -

Identifier Source: org_study_id

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