RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF (RELIEVE-HFrEF)

July 8, 2026 updated by: V-Wave Ltd

This study will evaluate the V-Wave Ventura Interatrial shunt. The Shunt is a small, hourglass-shaped device implanted in the dividing wall (septum) between the right and left atria (top chambers) of the heart placed during a minimally invasive cardiac catheterization procedure. The hourglass shape of the device holds the Shunt in place. The small opening in the center allows a small amount of blood to flow (to be shunted) from the top left chamber to the top right chamber of the heart. By "shunting" this small amount of blood, the increased pressure in the left side of the heart is reduced, which is expected to reduce congestion in the lungs and improve your symptoms of heart failure.

A previous study, the REducing Lung congestIon symptoms using the v-wavE shunt in adVancEd Heart Failure (RELIEVE-HF) trial showed that implantation of an interatrial shunt device was safe. In that study, patients whose heart pumping function (left ventricular ejection fraction, or LVEF) was >40% did not have better HF outcomes, such as hospitalization or even death after getting the device. However, the study looked separately at the LVEF ≤40% group and found that patients with an LVEF ≤40% showed improvements in these HF outcomes, as well as fewer episodes of worsening HF requiring an artificial heart pump. This suggests the shunt may help people whose heart pump is reduced, but more information is needed. The purpose of this study is to add to the data on the safety and whether the shunt works in preventing worsening heart failure for patients with reduced pumping strength or LVEF ≤40% .

This study is a multi-center, randomized, patient and observer blinded trial, with three (3) patients randomized to received the shunt (Treatment arm) for every two (2) non-implant Placebo-Procedure (Control patients). A total of approximately 250 patients will be randomized. Patients and research staff managing patients after randomization will be blinded during follow-up for a minimum of 12 months to a maximum of 24 months. All patients (Randomized to Treatment and Control) will be followed for a total of 3 years from the time of the randomization for comparison. Follow-up visits will be performed for the study will be conducted in clinic with the research doctors and staff and will include some telephone/remote visits. Patients randomized to the Control group who still meet inclusion/without exclusion criteria and consent will have an opportunity to receive the shunt if the effectiveness endpoint is met at primary study results.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The Study Device, the V-Wave Interatrial Shunt System, includes a permanent implant-the Shunt, placed during a minimally invasive cardiac catheterization procedure using its dedicated Delivery Catheter. By transferring blood from the left to the right atrium, the Shunt is intended to reduce excessive left-sided cardiac filling pressures in patients with advanced Heart Failure with reduced Ejection Fraction (HFrEF). The anticipated outcome is a reduction in heart failure events (all-cause mortality, cardiac transplantation or LVAD implantation (HT/LV), and all heart failure hospitalizations).

The study is a prospective, multi-center, 3:2 randomized, patient and observer blinded trial, with three (3) patients randomized to the Shunt Treatment arm for every two (2) non-implant Placebo-Procedure Control patients. The primary analysis will be performed when the last enrolled patient has been followed for a minimum of 12 months from randomization. The duration of follow-up evaluated by the primary effectiveness endpoint will range from a minimum of 12 to a maximum of 24 months. All patients (Randomized to Treatment and Control) will be followed for a total of 3 years from the time of the randomization. Patients randomized to the Control group who still meet inclusion/without exclusion criteria will have an opportunity to crossover and receive the shunt if the primary effectiveness endpoint is met at primary study analysis.

The REducing Lung congestIon symptoms using the v-wavE shunt in adVancEd Heart Failure (RELIEVE-HF) trial demonstrated that transcatheter implantation of an interatrial shunt device was safe but did not improve outcomes in HF patients across the full range of left ventricular ejection fraction (LVEF). However, results from a prespecified exploratory analysis in stratified randomized LVEF subgroups (LVEF ≤40% versus >40%) suggests that shunt implantation was beneficial in patients with reduced LVEF ≤40%. The RELIEVE- HFrEF trial is designed to provide additional data supporting this finding from the RELIEVE-HF trial.

Study Type

Interventional

Enrollment (Estimated)

250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Deborah Deutsch, VP of Clinical Affairs
  • Phone Number: 818-629-2164
  • Email: ddeutsch@its.jnj.com

Study Contact Backup

  • Name: Cheryl Calhoun RN, MS, Clinical Trial Manager
  • Phone Number: 603-493-3435
  • Email: ccalhou4@its.jnj.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Heart failure with a reduced LV ejection fraction (≤40%) and documented heart failure for at least 6 months from Baseline Visit.
  2. NYHA Class III symptoms

  3. Receiving guideline directed medical therapy (GDMT) for heart failure which refers to those HF drugs carrying a Class I indication:

    1. An inhibitor of the renin-angiotensin system (RAS inhibitor), including an angiotensin receptor-neprilysin inhibitor (ARNI), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and an evidence-based beta-blocker (BB) for at least 3 months prior to the Baseline Visit
    2. An SGLT2I Inhibitor for at least 1 month prior to the Baseline Visit
    3. Other medications recommended for selected populations, e.g., on diuretics as required for volume control. Mineralocorticoid receptor antagonist (MRA) or nitrates/hydralazine should be used in appropriate patients, according to the published guidelines.
    4. All patients are on stable HF medications as determined by the investigator, for at least 1 month, with the exception of diuretic therapy. Stable is defined as no more than a 100% increase or 50% decrease in dose within these periods.
  4. Receiving Class I recommended cardiac rhythm management device therapy. Specifically: if indicated by class I guidelines, cardiac resynchronization therapy (CRT), implanted cardioverter-defibrillator (ICD) or a pacemaker should be implanted at least 3 months prior to Baseline Visit.

  5. Must meet 5a OR 5b.

    1. One (1) prior Heart Failure Hospitalization with duration >24 hours or Emergency Room Heart Failure Visit with duration ≥6 hours, or Heart Failure Clinic ADHF Visit with duration ≥6 hours, within 12 months from Baseline Visit.
    2. Alternatively, if patients have not had a HF hospitalization or ER HF Visit within the prior 12 months, they must have a BMI corrected elevated Brain Natriuretic Peptide (BNP) level of at least 300 pg/ml or an N-terminal pro-BNP (NT-proBNP) level of at least 1,500 pg/ml, according to local measurement, within 3 months of the Baseline Visit.
  6. Able to perform the 6-minute walk test with a distance ≥100 meters and ≤450 meters.
  7. Provide written informed consent for study participation and be willing and able to comply with the required tests, treatment instructions and follow-up visits.

Main Exclusion Criteria:

  • Resting systolic blood pressure <90 or >160 mmHg
  • Baseline echocardiographic evidence of intracardiac blood clot, significant right ventricular dysfunction or severe left sided dilation.
  • Diagnosis of severe pulmonary hypertension.
  • Congenital Atrial septal defect, patent foramen ovale, with known shunting on echo
  • Untreated moderately severe or severe aortic or mitral stenosis.
  • Mitral valve repair device (e.g. MitraClip) implanted within 3 months prior to Baseline Visit.
  • Acute MI, acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), rhythm management system revision (not including generator change), lead extraction, or cardiac or other major surgery within 3 months of Baseline Visit.
  • Stroke, transient ischemic attack (TIA), systemic or pulmonary thromboembolism, or deep vein thrombosis (DVT) within 6 months.
  • Intractable HF with any of the following:

Treatment with IV vasoactive medications (e.g., IV inotropes, IV vasodilators) within the last 30 days.

Treated with a ventricular assist device (VAD). Listed for cardiac transplantation.

  • Prior cardiac transplantation.
  • Life expectancy <1 year due to non-cardiovascular illness.
  • Kidney failure or is receiving dialysis.
  • Active infection requiring parenteral or oral antibiotics.
  • Known allergy to nickel.
  • Hemodynamic, heart rhythm or respiratory instability at the time of Final Exclusion Criteria.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment arm
Treatment arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility followed by a transseptal catheterization and V-Wave Ventura interatrial shunt implantation and continue taking guideline recommended medical therapy .
Device: Implantation of the V-Wave Interatrial shunt
Implantation of the Ventura Shunt should be performed only by physicians experienced in transseptal cardiac catheterization procedures and trained in the proper use of the Shunt and Delivery System. Perform a standard right heart catheterization and (TEE) or (ICE) echo imaging to assess adequacy of vascular access, cardiovascular anatomy and to rule out potential contraindications. Perform a transseptal puncture, attempting to cross near the center of the fossa ovalis or where anatomy is most suitable. Advance the Delivery System and verify the tip is in the mid left atrium. Deploy the left portion of the Shunt which will be visible on echo or fluoroscopy. Slowly retract the Introducer and the Delivery System as a unit, until the left atrial cone of the Shunt contacts the left side of the fossa ovalis. Release the shunt from the delivery system, and retract until the Shunt is deployed across the fossa ovalis. Shunt placement is verified by fluoroscopic and echo observations.
Other Names:
  • V-Wave Ventura interatrial shunt
  • V-Wave shunt
  • Interatrial shunt implant
  • transseptal shunt
Sham Comparator: Control
Control arm patients will undergo a diagnostic right heart catheterization and invasive echocardiography to determine study eligibility, but will not have a transseptal catheterization and V-Wave Ventura interatrial shunt implantation and will continue guideline recommended medical therapy.
Device: Sham (no implant)
Study procedures should be performed only by physicians experienced in the RELIEVE-HFrEF study protocol and manual of operations. Perform a standard right heart catheterization and transesophogeal (TEE) or intracardiac (ICE) echo imaging to assess adequacy of vascular access, cardiovascular anatomy and to rule out potential contraindications. If eligible and randomized to control, the transseptal and shunt implantation will not be performed but the Interventionalist will simulate the procedure to maintain participant blinding.
Other Names:
  • Sham Control
  • No implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Safety
Time Frame: From enrollment at the intervention procedure through 30 days.
The percentage of Treatment Group patients experiencing device-related Major Adverse Cardiovascular and Neurological Events (MACNE) during the first 30 days after randomization, compared to a pre-specified Performance Goal.
From enrollment at the intervention procedure through 30 days.
Primary Effectiveness
Time Frame: The Primary analysis will be conducted after the final enrolled participant completes the 12-month visit. Data for the primary analysis will be collected from a minimum of 12- months to a maximum of 24-months of follow-up.

A composite of time to all-cause mortality or Heart Transplantation/LVAD implantation (HT/LV) and recurrent heart failure hospitalizations. This endpoint will be evaluated utilizing a Bayesian joint frailty model with two components: 1) time to all- cause mortality or HT/LV; and 2) rate of recurrent heart failure hospitalization. A shared parameter for the risk ratio will quantify the treatment benefit of Treatment versus Control across both components.

The primary analysis model will also incorporate Bayesian borrowing on the shared treatment effect from the corresponding subgroup in the RELIEVE-HF trial (≤40%). The prior information will be down weighted using Bayesian power prior methodology, and simulations will be used to calibrate the decision criteria and weighting of the prior information to be pre-specified in the Statistical Analysis Plan. This includes a comprehensive evaluation of statistical power and Type I error of the primary analysis with Bayesian borrowing.
The Primary analysis will be conducted after the final enrolled participant completes the 12-month visit. Data for the primary analysis will be collected from a minimum of 12- months to a maximum of 24-months of follow-up.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Secondary Effectiveness
Time Frame: Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Heart failure hospitalizations adjusted for all-cause mortality and HT/LV by joint frailty
Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Secondary Effectiveness
Time Frame: Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Primary endpoint inclusive of worsening HF treated as an outpatient (WHF)
Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Secondary Effectiveness
Time Frame: Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Primary endpoint replacing HFH with All-cause hospitalization (non-elective)
Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Secondary Effectiveness
Time Frame: Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Time to all-cause death or HT/LV
Baseline to the time of primary (unblinded) follow-up. Follow-up duration at outcome analysis ranges from a minimum of 12 months to a maximum of 24 months.
Secondary Effectiveness
Time Frame: Baseline to 12 months
Change in NYHA Class
Baseline to 12 months
Secondary Effectiveness
Time Frame: Baseline to 24 months
Change in NYHA Class
Baseline to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

V-Wave Ltd

Collaborators

Johnson & Johnson

Investigators

  • Principal Investigator: Michael Zile, MD, Medical University of South Carolina
  • Principal Investigator: Joann Lindenfeld, MD, Vanderbilt University
  • Principal Investigator: Gregg W. Stone, MD, Icahn School Of Medicine At Mount Sinai
  • Study Director: William T Abraham, MD, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 30, 2026

Primary Completion (Estimated)

March 31, 2029

Study Completion (Estimated)

September 30, 2031

Study Registration Dates

First Submitted

June 25, 2026

First Submitted That Met QC Criteria

July 8, 2026

First Posted (Actual)

July 10, 2026

Study Record Updates

Last Update Posted (Actual)

July 10, 2026

Last Update Submitted That Met QC Criteria

July 8, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL-5787

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

This decision balances participant privacy, ethical commitments in the consent process, legal/regulatory constraints, and the need to ensure scientific integrity. Aggregate results and study metadata will be made available; limited, controlled access to de-identified data may be provided under strict governance when appropriate.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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