Heart Failure and Reduced Ejection FractionRELIEVE-HFrEFNCT07696975
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
A study testing Implantation of the V-Wave Interatrial shunt in people with Heart Failure and Reduced Ejection Fraction and Heart Failure Chronic, run by V-Wave Ltd.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic, Heart Failure New York Heart Association Class III
- What is being tested?
- Implantation of the V-Wave Interatrial shunt
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2026to 30 Sep 2031
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 31Show fewer
- 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.
- 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.
Who cannot join
None listed.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the 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.
- Conditions
- Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic, Heart Failure New York Heart Association Class III, Heart Failure Congestive
- Being tested
- Implantation of the V-Wave Interatrial shunt, Sham (no implant)
- Keywords
- Heart Failure, Chronic heart failure, Reduced LVEF, Heart failure with low EF, interatrial shunt
- Medical subject headings
- Heart Failure, Systolic, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implantation of the V-Wave Interatrial shuntDevice
Also called V-Wave Ventura interatrial shunt, V-Wave shunt, Interatrial shunt implant, transseptal 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.
Sham (no implant)Device
Also called Sham Control, 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.
| Study group | Role | What they receive |
|---|---|---|
| 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 . Receives: 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. Receives: Device: Sham (no implant) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Heart failure hospitalizations adjusted for all-cause mortality and HT/LV by joint frailty
Measured: 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
Primary endpoint inclusive of worsening HF treated as an outpatient (WHF)
Measured: 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
Primary endpoint replacing HFH with All-cause hospitalization (non-elective)
Measured: 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 to all-cause death or HT/LV
Measured: 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
Change in NYHA Class
Measured: Baseline to 12 months
Secondary Effectiveness
Change in NYHA Class
Measured: Baseline to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study start30 Sep 2026 (estimated)
- Primary completion31 Mar 2029 (estimated)
- Study completion30 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Heart Failure and Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 (3:2)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- V-Wave Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson
- Responsible party
- Sponsor
- Investigators
- Gregg W. Stone, MD, Principal investigator, Icahn School of Medicine at Mount SinaiJoann Lindenfeld, MD, Principal investigator, Vanderbilt UniversityMichael Zile, MD, Principal investigator, Medical University of South CarolinaWilliam T Abraham, MD, Study director, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07696975
- Sponsor's protocol ID
- CL-5787
- Acronym
- RELIEVE-HFrEF
- Status last verified
- Jul 2026
- First submitted
- 25 Jun 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided: 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.
Publications
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.
PubMed 38773938Rodes-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.
PubMed 38561314Zile 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 40892630Stone 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
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
- ClinicalTrials.gov ID
- NCT07696975
- Acronym / sponsor ID
- RELIEVE-HFrEF / CL-5787
- Conditions
- Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic, Heart Failure New York Heart Association Class III, Heart Failure Congestive
- Keywords
- Heart Failure, Chronic heart failure, Reduced LVEF, Heart failure with low EF, interatrial shunt
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- V-Wave LtdIndustry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson
- Study start
- 30 Sep 2026 (estimated)
- Primary completion
- 31 Mar 2029 (estimated)
- Study completion
- 30 Sep 2031 (estimated)
- First posted
- 10 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized treatment versus control (3:2)
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Device: Implantation of the V-Wave Interatrial shuntTreatment 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 . |
| Control | Sham comparator | Device: Sham (no implant)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- 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:
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Implantation of the V-Wave Interatrial shuntAlso: V-Wave Ventura interatrial shunt, V-Wave shunt, Interatrial shunt implant, transseptal shuntImplantation 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. | Device | Treatment arm |
| Sham (no implant)Also: Sham Control, No implantStudy 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. | Device | Control |
Primary outcome
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.
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.
6 secondary outcomes
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.
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.
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.
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.
Secondary Effectiveness
Time frame: Baseline to 12 months
Secondary Effectiveness
Time frame: Baseline to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Background: PubMed 38773938Pfeiffer 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.
- Background: PubMed 38561314Rodes-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.
- Background: PubMed 40892630Zile 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.
- Background: PubMed 39308371Stone 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.
- Individual participant dataSharing planned: Undecided. 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.
Related trials for Heart Failure and Reduced Ejection Fraction
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07328948 in Adults With Heart Failure (BRANCH-HF)
Heart Failure
RecruitingPhase 3
Qishen Yiqi Dripping Pills in Treatment of Chronic Heart FailUre
Heart Failure
RecruitingPhase 1/2
Endocardial Delivery for Myocardial Regeneration Using Allogeneic iPSC-derived Cardiomyocyte Spheroids for HF With Systolic Dysfunction (EMERALD Study)
Heart Failure, Ischemic Heart Failure
Recruiting
Evaluation of the Effects of Sauna Therapy on Congestion and Loop Diuretic Use in Patients With Heart Failure With Reduced or Moderately Reduced Ejection Fraction
Heart Failure
Not yet recruiting
Exercise, Mediterranean Diet and Inflammation in Heart Failure
Heart Failure, Heart Failure Preserved Ejection Fraction
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gregg W. Stone, MD principal investigator
Icahn School of Medicine at Mount Sinai
Joann Lindenfeld, MD principal investigator
Vanderbilt University
Michael Zile, MD principal investigator
Medical University of South Carolina
Questions about this trial
What is this clinical trial studying?
A study testing Implantation of the V-Wave Interatrial shunt in people with Heart Failure and Reduced Ejection Fraction and Heart Failure Chronic, run by V-Wave Ltd.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 0 exclusion criteria. 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: opening soon, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Contact Deborah Deutsch, VP of Clinical Affairs (818-629-2164, ddeutsch@its.jnj.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Safety (time frame: From enrollment at the intervention procedure through 30 days.). 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 NCT07696975, 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 10 Jul 2026.