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

NCT07696975 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: CL-5787
• Study Type: interventional
• Target: 250
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Heart Failure and Reduced Ejection Fraction; Heart Failure Chronic; Heart Failure Congestive; Heart Failure New York Heart Association Class III

Keywords

Heart Failure; Chronic heart failure; Reduced LVEF; Heart failure with low EF; interatrial shunt

Outcome Measures

Primary Outcomes (2)

• Primary Safety

  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

  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 Outcomes (6)

• Secondary Effectiveness

  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

  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

  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

  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

  Baseline to 12 months

Study Arms (2)

Treatment arm

EXPERIMENTAL

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

Control

SHAM COMPARATOR

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)

Interventions

Implantation of the V-Wave Interatrial shunt DEVICE

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.

Also known as: V-Wave Ventura interatrial shunt, V-Wave shunt, Interatrial shunt implant, transseptal shunt

Treatment arm

Sham (no implant) DEVICE

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.

Also known as: Sham Control, No implant

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Heart failure with a reduced LV ejection fraction (≤40%) and documented heart failure for at least 6 months from Baseline Visit.
• NYHA Class III symptoms
• Receiving guideline directed medical therapy (GDMT) for heart failure which refers to those HF drugs carrying a Class I indication:
• 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
• An SGLT2I Inhibitor for at least 1 month prior to the Baseline Visit
• 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.
• 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.
• 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.
• Must meet 5a OR 5b.
• 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.
• 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.
• Able to perform the 6-minute walk test with a distance ≥100 meters and ≤450 meters.
• Provide written informed consent for study participation and be willing and able to comply with the required tests, treatment instructions and follow-up visits.

You may not qualify if:

• 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.

Sponsors & Collaborators

• V-Wave Ltd: lead
• Johnson & Johnson: collaborator

Related Publications (4)

• Pfeiffer M, Boehmer J, Gorcsan J, Eguchi S, Orihara Y, Perl ML, Eigler N, Abraham WT, Villota JN, Lee E, Bayes-Genis A, Moravsky G, Kar S, Zile MR, Holcomb R, Anker SD, Stone GW, Rodes-Cabau J, Lindenfeld J, Bax JJ. In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure. ESC Heart Fail. 2024 Oct;11(5):2499-2509. doi: 10.1002/ehf2.14859. Epub 2024 May 22.

  PMID: 38773938 BACKGROUND

• Rodes-Cabau J, Lindenfeld J, Abraham WT, Zile MR, Kar S, Bayes-Genis A, Eigler N, Holcomb R, Nunez J, Lee E, Perl ML, Moravsky G, Pfeiffer M, Boehmer J, Gorcsan J, Bax JJ, Anker S, Stone GW. Interatrial shunt therapy in advanced heart failure: Outcomes from the open-label cohort of the RELIEVE-HF trial. Eur J Heart Fail. 2024 Apr;26(4):1078-1089. doi: 10.1002/ejhf.3215. Epub 2024 Apr 1.

  PMID: 38561314 BACKGROUND

• 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.

  PMID: 40892630 BACKGROUND

• 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.

  PMID: 39308371 BACKGROUND

MeSH Terms

Conditions

Heart Failure, Systolic; Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Gregg W. Stone, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Joann Lindenfeld, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

• Michael Zile, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

• William T Abraham, MD

  Ohio State University

  STUDY DIRECTOR

Central Study Contacts

Deborah Deutsch, VP of Clinical Affairs

CONTACT

818-629-2164; ddeutsch@its.jnj.com

Cheryl Calhoun RN, MS, Clinical Trial Manager

CONTACT

603-493-3435; ccalhou4@its.jnj.com

Study Design

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

Model Details: Randomized treatment versus control (3:2)

Study Record Dates

• First Submitted: June 25, 2026
• First Posted: July 10, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): September 30, 2031
• Last Updated: July 10, 2026

Record last verified: 2026-07