Feasibility Study to Support Cardiorenal Function in Acute Decompensated Heart Failure With Diuretic Resistance

Study Overview
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Brief Summary
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Evaluation of the safety and efficacy of the ModulHeart System in patients hospitalized with acute decompensated heart failure (ADHF) and diuretic resistance

Detailed Description
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The study is a prospective, single-arm, non-randomized feasibility study to evaluate the safety and performance of the ModulHeart System in patients hospitalized with ADHF and diuretic resistance. The ModulHeart system consists of the ModulHeart Delivery System, the ModulHeart Pumps, the ModulHeart Controller, and the ModulHeart Retrieval System.

Official Title
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Early Feasibility Study to Mechanically Support Cardiorenal Function in Acute Decompensated Heart Failure With Diuretic Resistance

Conditions
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Cardiorenal Syndrome, Heart Failure, Acute Decompensated Heart Failure, Heart Failure, Congestive, Heart Failure With Preserved Ejection Fraction, Heart Failure With Reduced Ejection Fraction, Diuretic Resistance

Intervention / Treatment
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* Device: ModulHeart Support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to the hospital with a primary diagnosis of ADHF Clinical signs and/or symptoms of congestion defined as at least one of the following: dyspnea at rest or with minimal exertion, orthopnea, lower extremity edema (≥2+), elevated jugular venous pressure, pulmonary rales, pulmonary vascular congestion on chest x-ray, pleural effusion or ascites Projected need by the treating clinician for continued treatment with IV diuretic agents for more than 48 hours with the goal of significant fluid removal (more than 1L net fluid loss/24h) Appropriate intravenous loop diuretic therapy at the time of enrollment, defined as at least the higher of: Furosemide 40mg IV bid or equivalent IV furosemide or equivalent IV loop diuretic equivalent to ≥2x the total oral daily loop diuretic dose at home in 2 divided doses Diuretic resistance defined as at least ONE of the following: Urine output of less than 1.5L over 12h following the last diuretic dose, OR Net fluid loss of less than 1L over the last 24 hours, OR Spot urinary sodium concentration of less than 70 mmol/L 2h following the last diuretic dose or cumulative 6-hour natriuresis of less than 100 mmol following the last diuretic dose, OR Clinically unsatisfactory resolution of congestion Age ≥ 21 years old Signed informed consent Exclusion Criteria: ADHF related to acute secondary disease (i.e., infection or acute coronary syndrome) Treatment with high dose inotropes (milrinone ≥0.375 mcg/kg/min, dobutamine ≥5mcg/kg/min or dopamine ≥5mcg/kg/min) and/or treatment with vasopressors to maintain a systolic arterial blood pressure ≥90 mmHg or mean arterial blood pressure ≥60 mmHg Current or previous support with a durable left ventricular assist device (LVAD) at any time or use of an extracorporeal membrane oxygenation (ECMO), percutaneous ventricular assist devices, intra-aortic balloon pump or patient on home inotropes currently or within the last 30 days Recent myocardial infarction, percutaneous coronary intervention or surgical revascularization (within the last 3 months) or awaiting planned coronary intervention or surgery Fixed pulmonary vascular resistance of more than 5 Wood units, estimated PASP of more than 80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure Prior heart transplant, heart failure due to rejection of a previous heart transplant, or planned heart transplantation Reanimated cardiac arrest in the last 30 days Suspected or known amyloid disease or other restrictive cardiomyopathy Severe bleeding risk precluding anticoagulation: Previous intracranial bleed unless there is documentation in the medical record (from a physician that is not part of the study) that the patient can safely use anticoagulation for 7 days Gastrointestinal (GI) bleeding within 1 month requiring hospitalization and/or transfusion Recent major surgery within 1 month if the surgical wound is judged to be associated with an increased risk of bleeding Platelet count of less than 50,000 cells/mm3 Uncorrectable bleeding diathesis or coagulopathy Contraindicated anatomy: Descending aortic anatomy that would prevent safe placement of the device (less than 18 mm or more than 28mm thoracoabdominal aorta diameter at deployment location) Abnormalities of the aorta or subclavian or axillary arteries that would prevent safe device placement, including aneurysms, significant tortuosity, or calcifications Axillary artery anatomy that would preclude safe placement of a 10F sheath including severe obstructive calcification or severe tortuosity Iliofemoral artery anatomy that would preclude safe placement of a 16F introducer sheath including severe obstructive calcification or severe tortuosity Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury Prior endovascular surgery or percutaneous intervention involving the thoracoabdominal aorta or a subclavian/axillary artery or history of aortic dissection Severe aortic stenosis Known or suspected contrast induced nephropathy Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication Absolute contraindications or allergy to unfractionated heparin (e.g., heparin-induced thrombocytopenia) or device materials (e.g. nickel, titanium) that cannot be adequately treated with pre-medication Known hematologic diseases such as leukemia, any coagulopathy or hypercoagulable state, sickle cell anemia or thalassemia Presence of any one of the following risk factors for indications of severe end organ dysfunction or failure: Liver disease (cirrhosis of the liver [Child-Pugh class B or C]) or shock liver History of severe chronic obstructive pulmonary disease (COPD) defined by FEV1/FVC less than 0.7, and FEV1 less than 50% predicted Prior kidney transplant, isolated single kidney, stage V Chronic Kidney Disease (eGFR ≤15) at admission OR use of dialysis, continuous renal replacement therapy (CRRT) or aquapheresis (ultrafiltration) in last 90 days Cardiac imaging evidence of intracardiac mass, thrombus, or vegetation Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 90 days prior to the index procedure Active infection not controlled with antibiotic therapy Suspected or known pregnancy. Women of child-bearing age should have a negative pregnancy test. Body mass index (BMI) over 40 kg/m2 Estimated life expectancy of less than 6 months Unable or unwilling to undergo screening, device implant and retrieval procedures, and 30-day follow-up Currently participating in an investigational drug or another device study that may influence the data collected for this study. Observational studies are not considered an exclusion Subject has other medical, social or psychological problems that, in the opinion of the Investigator, compromises the subject ability to give written informed consent and/or to comply with study procedures Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments

Ages Eligible for Study
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Minimum Age: 21 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ModulHeart System<br> | Device: ModulHeart Support<br>* The ModulHeart device will be implanted in the descending abdominal aorta.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device safety defined as freedom from serious in-hospital procedure or device-related adverse event (AE) |  | Baseline to 30-day Follow-Up | 
| Technical success defined as successful device deployment, ability to deliver the treatment and remove the device |  | Baseline to 30-day Follow-Up | 
| Assisted decongestion success defined as increase in the average hourly rate of urine output during the first 24 hours of ModulHeart-assisted decongestive therapy compared to the last 24 hours of diuretic therapy prior to pump implant |  | Baseline to 1 day of ModulHeart-assisted decongestive therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine output |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in net fluid loss |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in natriuresis |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in creatinine clearance |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in N-terminal pro-B type natriuretic peptide (NT-pro BNP) |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in body weight |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in thermodilution cardiac output |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in right atrial pressure |  | Baseline to end of ModulHeart therapy (up to 7 days) | 
| Change in mean pulmonary artery pressure |  | Baseline to end of ModulHeart therapy (up to 7 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MCS, Puzzle Medical Devices, ModulHeart, Mechanical Circulatory Support, Intra-Aortic, LVAD, pVAD, percutaneous ventricular assist device, Left ventricular assist device