Reducing Lung CongestIon Symptoms in Advanced Heart Failure

Study Overview
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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.

Official Title
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RELIEVE-HF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Device: V-Wave Interatrial Shunt
* Other: Control


Participation Criteria
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Eligibility Criteria
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Main 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 Main 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 Hemodynamic heart rhythm, or respiratory instability at time of Final Exclusion Criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>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<br>* 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.<br>|
| Other: Control<br>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<br>* Right heart catheterization, invasive echocardiography.<br>|
| Experimental: Roll in<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6MWT changes | 6MWT changes | Baseline to 12 months | 
| KCCQ changes | KCCQ changes | Baseline to 12 months | 
| KCCQ changes | KCCQ changes | Baseline through study completion, maximum of five years | 
| Time to all-cause death, LVAD/Transplant, or heart failure hospitalization | 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 | Time to all-cause death or first heart failure hospitalization | Baseline through study completion, maximum of five years | 
| Cumulative heart failure hospitalizations | Cumulative heart failure hospitalizations | Baseline through study completion, maximum of five years | 
| Time to first heart failure hospitalization | Time to first heart failure hospitalization | Baseline through study completion, maximum of five years | 
| Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ | Modified Primary Effectiveness Endpoint including all-cause death, LVAD/Transplant, HF Hospitalizations, and worsening HF events treated as outpatient but without KCCQ | Baseline through study completion, maximum of five years |