NCT03499236

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
605

participants targeted

Target at P75+ for not_applicable heart-failure

Timeline
18mo left

Started Sep 2018

Longer than P75 for not_applicable heart-failure

Geographic Reach
11 countries

83 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Sep 2018Oct 2027

First Submitted

Initial submission to the registry

March 29, 2018

Completed
19 days until next milestone

First Posted

Study publicly available on registry

April 17, 2018

Completed
5 months until next milestone

Study Start

First participant enrolled

September 19, 2018

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 9, 2023

Completed
4.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2027

Expected
Last Updated

August 19, 2025

Status Verified

November 1, 2024

Enrollment Period

5.1 years

First QC Date

March 29, 2018

Last Update Submit

August 18, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (8)

  • 6MWT changes

    Baseline to 12 months

  • KCCQ changes

    Baseline to 12 months

  • KCCQ changes

    Baseline through study completion, maximum of five years

  • 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

    Baseline through study completion, maximum of five years

  • +3 more secondary outcomes

Study Arms (3)

Treatment

EXPERIMENTAL

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

Control

OTHER

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

EXPERIMENTAL

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

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.

Roll inTreatment
ControlOTHER

Right heart catheterization, invasive echocardiography.

Control

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (83)

Abrazo Arizona Heart Hospital

Phoenix, Arizona, 85016, United States

Location

Arizona Heart Rhythm Center

Phoenix, Arizona, 85016, United States

Location

Scripps Health

La Jolla, California, 92037, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Keck Medical Center of USC

Los Angeles, California, 90033, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90211, United States

Location

Kaiser Permanente San Francisco

San Francisco, California, 94118, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford Hospital

Stanford, California, 94305, United States

Location

Los Robles Hospital & Medical Center

Thousand Oaks, California, 91360, United States

Location

The Lundquist Institute (Harbor-UCLA) Medical Center

Torrance, California, 90502, United States

Location

South Denver Cardiology

Littleton, Colorado, 80120, United States

Location

Memorial Hospital

Jacksonville, Florida, 32216, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

First Coast Cardiovascular Institute

Orange Park, Florida, 32003, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Midwest Cardiovascular Institute

Naperville, Illinois, 60540, United States

Location

St Elizabeth Medical Center

Edgewood, Kentucky, 41017, United States

Location

United Heart & Vascular Clinic

Saint Paul, Minnesota, 55102, United States

Location

Nebraska Heart Institute

Lincoln, Nebraska, 68526, United States

Location

Valley Health System

Ridgewood, New Jersey, 07450, United States

Location

Weill Cornell

New York, New York, 10065, United States

Location

Rochester General Health System

Rochester, New York, 14621, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, United States

Location

North Carolina Heart & Vascular

Raleigh, North Carolina, 27607, United States

Location

Summa Health

Akron, Ohio, 44304, United States

Location

Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 80120, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

UPMC Pinnacle / Pinnacle Health Cardiovascular Institute

Wormleysburg, Pennsylvania, 17043, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

Austin Heart

Austin, Texas, 78756, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Texas Heart Institute

Houston, Texas, 77030, United States

Location

University of Texas Memorial Hermann

Houston, Texas, 77030, United States

Location

Methodist Hospital

San Antonio, Texas, 78249, United States

Location

Christus Mother Frances Hospital

Tyler, Texas, 75701, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Chippenham Medical Center

Richmond, Virginia, 23225, United States

Location

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Flinders Medical Centre

Adelaide, Australia

Location

Prince Charles Hospital

Brisbane, Australia

Location

St. Vincent's Hospital

Melbourne, Australia

Location

Ziekenhuis Aan De Stroom vzw (ZAS)

Antwerp, Belgium

Location

AZ Sint-Jan Brugge

Bruges, Belgium

Location

Montréal Heart Institute

Montreal, Canada

Location

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

Québec, G1V 4G5, Canada

Location

Charité - Universitätsmedizin Berlin Campus Virchow-Klinikum

Berlin, 10117, Germany

Location

Vivantes Klinikum im Friedrichshain

Berlin, 10249, Germany

Location

Vivantes Klinikum Urban

Berlin, Germany

Location

Marienkrankrankenhas

Hamburg, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Herzzentrum Leipzig

Leipzig, 04289, Germany

Location

Ludwig-Maximilians-Universität München

München, 81377, Germany

Location

SANA Remscheid

Remscheid, Germany

Location

University of Rostock

Rostock, Germany

Location

University Hospital Samson Assuta Ashdod

Ashdod, 7747629, Israel

Location

Yitzhak Shamir Medical Center

Be’er Ya‘aqov, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

The Chaim Sheba Medical Center Tel-Hashomer

Ramat Gan, 52621, Israel

Location

Kaplan Medical Center

Rehovot, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

The Baruch Padeh Medical Center, Poriya

Tiberias, 15208, Israel

Location

St Antonius Ziekenhuis Nieuwegein

Nieuwegein, Utrecht, 3435, Netherlands

Location

Academic Medical Center, The Netherlands

Amsterdam, 1105, Netherlands

Location

Erasmus University Medical Center Rotterdam

Rotterdam, 3015, Netherlands

Location

Christchurch Hospital

Christchurch, New Zealand

Location

Institute of Cardiology, Warsaw

Warsaw, Poland

Location

The 4th Military Clinical Hospital Wroclaw

Wroclaw, Poland

Location

University Hospital Wroclaw

Wroclaw, Poland

Location

Hospital Clinic of Barcelona

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitari Germans Trias i Pujol, Badalona Barcelona

Barcelona, 08916, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Puerta de Hierro-Majadahonda

Madrid, 28222, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47003, Spain

Location

Bern University Hospital

Bern, 3010, Switzerland

Location

University Hospital of Zürich

Zurich, 8091, Switzerland

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
In the randomized cohort, participants, the clinical team, and research staff managing the patient after randomization will be blinded to study assignment.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 29, 2018

First Posted

April 17, 2018

Study Start

September 19, 2018

Primary Completion

October 9, 2023

Study Completion (Estimated)

October 31, 2027

Last Updated

August 19, 2025

Record last verified: 2024-11

Data Sharing

IPD Sharing
Will share

Locations