Diuretics Alone vs. Aortix Endovascular Device for Acute Heart Failure

Study Overview
=================
Brief Summary
-----------------
Aortix is a circulatory support device for chronic heart failure patients on medical management who have been hospitalized for acute decompensated heart failure (ADHF) and are resistant to diuretic therapy. Eligible ADHF patients with diuretic resistance (irrespective of ejection fraction) will be enrolled and randomized 1:1 to either the Aortix system or standard of care medical management.

Detailed Description
-----------------
The study is a prospective, multi-center, randomized, nonblinded study to evaluate the safety and effectiveness of the Aortix System versus standard of care medical therapy in patients hospitalized with acute decompensated heart failure (ADHF) and persistent congestion despite usual medical management.Eligible ADHF patients with diuretic resistance (irrespective of ejection fraction) will be enrolled and randomized 1:1 to either the Aortix system or standard of care medical management. Randomization will be stratified by ejection fraction.. An additional registry arm will enroll patients who are considered candidates for advanced therapies in the near-term, but need improvement in their renal function to be able to receive additional medical therapies. All eligible enrolled registry subjects will receive Aortix system support. Planned study population is male or female patients 21 years of age or greater, with acute decompensated heart failure and diuretic resistance who remain congested despite standard of care medical therapy. This study will enroll up to 268 subjects with heart failure at 45 clinical sites in the United States. The randomized study includes up to 188 subjects and the Advanced HF registry includes up to 80 subjects.

Official Title
-----------------
DRAIN-HF: Diuretics Alone vs. Aortix Endovascular Device for Acute Heart Failure

Conditions
-----------------
ADHF, Heart Failure, Cardiorenal Syndrome, Cardio-Renal Syndrome, Heart Failure, Systolic, Heart Failure, Diastolic, Heart Failure; With Decompensation, Heart Failure, Congestive

Intervention / Treatment
-----------------
* Device: Aortix System


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (Randomized Study): Currently admitted to the hospital with a primary diagnosis of decompensated heart failure, irrespective of ejection fraction (EF); Urine output for 12 hours prior to enrollment is < 1500 ml following at least 48 hours of the higher of: i) furosemide 80 mg IV bid or equivalent or ii) IV furosemide or equivalent IV loop diuretic at a dose 2.5 x total daily home dose of furosemide equivalents in 2 divided doses, as tolerated; Persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema or ascites after treatment with IV diuretics per inclusion criterion 2.; Age >21 years and able to provide written informed consent; Negative pregnancy test if patient is of child-bearing potential. Exclusion Criteria (Randomized Study): Treatment with high dose IV inotropes within the last 48 hours. High dose is defined as >5 µg/kg/min dopamine OR >5 µg/kg/min dobutamine OR >0.375 µg/kg/min milrinone; Active and ongoing hypotension with a systolic blood pressure <90 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) <60 mmHg lasting more than 30 minutes; Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours of enrollment; An estimated PASP of >80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure; Treatment with IV diuretics (does not have to be continuous) for ≥21 days during the current hospitalization (including time spent at an outside hospital); Acute kidney failure defined as an increase in serum creatinine to ≥4.0mg/dL (≥353.6 µmol/L) within the last 48 hours before enrollment; Evidence of contrast induced nephropathy, nephritis or nephrotic syndrome; Prior kidney transplant, single kidney, partial nephrectomy, stage V chronic kidney disease (eGFR <18) at admission OR use of dialysis, continuous renal replacement therapy (CRRT) or ultrafiltration in the last 90 days; Confirmed cirrhosis or concern for shock liver (AST > 1000U/L or total Bilirubin > 5.0mg/dl); Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device; Prior heart transplant or likely heart transplantation before the 30- day follow-up visit; Current or previous support with a durable LVAD at any time or planned LVAD insertion before the 30-day follow-up visit; Use of an intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), or percutaneous ventricular assist devices (e.g. Impella or TandemHeart) within the last 30 days; Known amyloidosis of any type; Acute myocardial infarction Type 1 within 30 days of enrollment, or planned coronary revascularization in the next 30 days; Stroke within 30 days of enrollment; Severe Bleeding Risk (any of the following): 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, GI bleeding within 6 months requiring hospitalization and/or transfusion, Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding, Procedure with arterial ilio-femoral access > 6 FR within 30 days, Platelet count <75,000 cells/mm3, Uncorrectable bleeding diathesis or coagulopathy (e.g. INR ≥2 not due to anticoagulation therapy) or hypercoaguable state including HIT; Inability to tolerate anticoagulation therapy for up to 7 days. Contraindicated Anatomy : Descending aortic anatomy that would prevent safe placement of the device [<18 mm or >31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)], Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21F (outer diameter) introducer sheath, Femoral artery depth inconsistent with use of closure device, Abnormalities or severe vascular disease that would preclude safe access and device delivery (e.g. aneurysm with thrombus, marked tortuosity, significant narrowing or inadequate size of the abdominal aorta, iliac or femoral arteries, or severe calcification), Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury, Current endovascular stent graft in the descending aorta or any femoro-iliac vessels; Known hypersensitivity or contraindication to study or procedure medications (e.g. anticoagulation therapy) or device materials (e.g. history of severe reaction to nickel or nitinol); Participation in any other clinical investigation that is likely to confound study results or affect the study; Poor health such that the patient is unable to undergo the Aortix device placement/retrieval and/or unlikely to be able to survive to the 30-day visit; Unable or unwilling to undergo screening (imaging, PA Catheter placement), device implant and retrieval procedures or return for 30-day visit.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients will be randomized 1:1 and will be receiving their treatment in parallel to each other. An additional non-randomized registry is also included
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Eligible ADHF patients with diuretic resistance (irrespective of ejection fraction) will be enrolled and randomized 1:1 to either the Aortix system or standard of care medical management. Randomization will be stratified by ejection fraction. | Device: Aortix System<br>* Aortix is a circulatory support device for chronic heart failure patients on medical management who have been hospitalized for acute decompensated heart failure (ADHF) and are resistant to diuretic therapy.<br>* Other names: Aortix Pump;|
| No Intervention: Control Arm<br>The Control arm should receive standard of care therapy as per the study directed Diuretic Care Treatment Algorithm. | |
| Experimental: Advanced HF Registry<br>For the Advanced HF registry, all eligible enrolled subjects will receive Aortix system support. | Device: Aortix System<br>* Aortix is a circulatory support device for chronic heart failure patients on medical management who have been hospitalized for acute decompensated heart failure (ADHF) and are resistant to diuretic therapy.<br>* Other names: Aortix Pump;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Endpoint: Incidence of Aortix Device / Procedural-Related Major Adverse Events (MAE) through 30 days of Follow-up. | Incidence of Major Adverse Events | Baseline to 30 day Follow-Up | 
| Primary Effectiveness Endpoint: Combined composite of clinically significant reduction in net fluid loss over 7 days and freedom from mortality or heart failure re-hospitalization/therapy escalation from the baseline visit to the 30-day follow-up visit. | Composite of net fluid loss, mortality and HF hospitalization/escalation of therapy | Baseline to 30 day Follow-Up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net Fluid Loss | Change in Net Fluid Loss from Baseline to Day 7/Discharge | Baseline to Day 7 | 
| All-cause Mortality | Rate of mortality | Baseline to 30 day Follow-Up | 
| HF Re-Hospitalization or escalation of HF therapy | Evaluation of HF re-hospitalization and therapy escalation | Baseline to 30 day Follow-Up | 
| eGFR | Evaluation of changes in eGFR | Baseline to 30 day Follow-Up | 
| NT-proBNP | Evaluation of NT-proBNP | Baseline to 30 day Follow-Up | 
| Patient Reported Dyspnea Assessment | Change in patient reported dyspnea scale | Baseline to 30 day Follow-Up | 
| Standing body weight | Change in standing body weight | Baseline to 30 day Follow-Up | 
| Incidence and percentages of major adverse events (MAE) Pooled | Incidence and percentages of major adverse events (MAE) pooled analysis of Aortix randomized cohort and registry cohort | Baseline to 30 day Follow-Up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
mechanical circulatory support, percutaneous