Clinical trial NCT05677100: Diuretics Alone vs. Aortix Endovascular Device for Acute Heart Failure
Official title: DRAIN-HF: Diuretics Alone vs. Aortix Endovascular Device for Acute Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Cardiorenal Syndrome
Cardio-Renal Syndrome
ADHF
Heart Failure, Systolic
Heart Failure, Diastolic
Heart Failure; With Decompensation
Heart Failure, Congestive
Keywords: mechanical circulatory support
percutaneous
Lead sponsor: Procyrion
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 295
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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 have persistent congestion despite usual medical 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 295 subjects with heart failure at 45 clinical sites in the United States and up to 5 OUS sites. The randomized study includes up to 215 subjects and the Advanced HF registry includes up to 80 subjects.

Eligibility criteria: Inclusion Criteria (Randomized Study):

* Currently admitted to the hospital with a primary diagnosis of decompensated heart failure, irrespective of ejection fraction (EF);
* 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, patient must have: Urine Output \<1,500mL in a 12-hour period OR a Net Fluid Loss ≤375mL in a 12-hour period.
* Persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water 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 prior to enrollment. 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 at enrollment;
* Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to 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) at 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 enrollment OR use of dialysis, continuous renal replacement therapy (CRRT) or ultrafiltration in the last 90 days prior to enrollment;
* Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment;
* 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):

  1. 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,
  2. GI bleeding within 6 months requiring hospitalization and/or transfusion,
  3. Recent major surgery within 30 days if the surgical wound is judged to be associated with an increased risk of bleeding,
  4. Procedure with arterial ilio-femoral access \> 6 FR within 30 days,
  5. Platelet count \<75,000 cells/mm3,
  6. Uncorrectable bleeding diathesis or coagulopathy (e.g. INR ≥2 not due to anticoagulation therapy) or hypercoaguable state including HIT;
  7. Inability to tolerate anticoagulation therapy for up to 7 days.
* Contraindicated Anatomy :

  1. Descending aortic anatomy that would prevent safe placement of the device \[\<18 mm or \>31 mm aorta diameter at deployment location (measured between the superior aspect of the T10 vertebra and superior aspect of the L1 vertebra)\],
  2. Ilio-femoral diameter or peripheral vascular anatomy that would preclude safe placement of a 21F (outer diameter) introducer sheath,
  3. Femoral artery depth inconsistent with use of closure device,
  4. 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),
  5. Known connective tissue disorder (e.g. Marfan Syndrome) or other aortopathy at risk of vascular injury,
  6. Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging.
* 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.

Inclusion Criteria (Advanced Heart Failure Registry):

* Currently admitted to the hospital with a primary diagnosis of decompensated HF, irrespective of ejection fraction (EF).
* Patient has already been evaluated and indicated to receive an LVAD or heart transplant and will receive the LVAD or be listed for heart transplantation in the next 30 days if their congestion status and renal function improves.
* Patient must have been treated with ≥ 80 mg IV furosemide bid or equivalent and have evidence of increasing diuretic dosing requirements over the past 12 months, as tolerated.
* Must have evidence of refractoriness to medical management as documented by persistent signs and/or symptoms of congestion as evidenced by at least 2+ pitting edema, elevated jugular venous pressure \>12 cm water, or ascites after treatment with IV diuretics for a minimum of 24 hours.
* Serum creatinine ≥ 2.0 mg/dL AND eGFR ≤ 45 ml/min/1.73m2 at time of enrollment
* Age ≥ 21 years and able to provide written informed consent.
* Negative pregnancy test if patient is of childbearing potential.

Exclusion Criteria (Advanced Heart Failure Registry):

* Treatment with high dose IV inotropes within 48 hours prior to enrollment. High dose is defined as any one of the following: \>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 \<80 mmHg lasting more than 30 minutes or a mean arterial pressure (MAP) \<55 mmHg lasting more than 30 minutes at enrollment.
* Treatment with vasopressors (defined as phenylephrine, norepinephrine, epinephrine or, vasopressin) within 48 hours prior to enrollment.
* An estimated PASP of \>80 mmHg as measured on echocardiogram or echocardiographic evidence of primarily right heart failure.
* Acute kidney failure defined as an increase in serum creatinine to ≥ 4.0mg/dL at enrollment.
* Evidence of contrast-induced nephropathy, nephritis, or nephrotic syndrome.
* Prior kidney transplant, single kidney, partial nephrectomy, eGFR≤18 ml/min/1.73m2 at enrollment OR use of dialysis, continuous renal replacement therapy (CRRT), or ultrafiltration in the last 90 days prior to enrollment.
* Confirmed decompensated cirrhosis (defined as Child Pugh class B or C) or concern for shock liver (AST \> 1000U/L or total Bilirubin \> 5.0mg/dl) at enrollment.
* Presence of an active, uncontrolled infection that would preclude safe placement or removal of the device.
* Current or previous support with a durable LVAD.
* INTERMACS Profile 1 at enrollment.
* Currently on mechanical ventilatory support.
* Use of an intra-aortic balloon pump (IABP) within the last 14 days or use of an extracorporeal membrane oxygenation (ECMO) or percutaneous ventricular assist device (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 hypercoagulable 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 21 Fr (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.
  * Any endovascular stent graft in the descending aorta. Any endovascular stent graft in the femoro-iliac vessels that is not well endothelialized and would preclude safe introduction/removal of the Aortix pump as demonstrated by imaging.
* 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, device implant and retrieval procedures, or return for 30-day visit.

Primary outcomes:
measure: Primary Safety Endpoint: Incidence of Aortix Device / Procedural-Related Major Adverse Events (MAE) through 30 days of Follow-up.
timeFrame: Baseline to 30 day Follow-Up
measure: 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.
timeFrame: Baseline to 30 day Follow-Up
Secondary outcomes:
measure: Net Fluid Loss
timeFrame: Baseline to Day 7
measure: All-cause Mortality
timeFrame: Baseline to 30 day Follow-Up
measure: HF Re-Hospitalization or escalation of HF therapy
timeFrame: Baseline to 30 day Follow-Up
measure: eGFR
timeFrame: Baseline to 30 day Follow-Up
measure: NT-proBNP
timeFrame: Baseline to 30 day Follow-Up
measure: Patient Reported Dyspnea Assessment
timeFrame: Baseline to 30 day Follow-Up
measure: Standing body weight
timeFrame: Baseline to 30 day Follow-Up
measure: Incidence and percentages of major adverse events (MAE) Pooled
timeFrame: Baseline to 30 day Follow-Up
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Health Care System
state: Alabama
city: Phoenix
country: United States
facility: Banner--University Medical Center Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Medical Center
state: Arizona
city: Concord
country: United States
facility: John Muir Health
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General
state: California
city: San Francisco
country: United States
facility: San Francisco Veterans Administration
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Pensacola
country: United States
facility: Ascension Sacred Heart
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Tampa
country: United States
facility: BayCare Medical/St. Joseph's Hospital
state: Florida
city: Tampa
country: United States
facility: AdventHealth Tampa
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: Piedmont Healthcare Inc.
state: Georgia
city: Marietta
country: United States
facility: Wellstar Research Institue
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Chicago
country: United States
facility: Advocate IMMC
state: Illinois
city: Downers Grove
country: United States
facility: Advocate Aurora - Good Samaritan
state: Illinois
city: Wichita
country: United States
facility: Ascension via Christi Kansas
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan, Cardiovascular Medicine
state: Michigan
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Brooklyn
country: United States
facility: New York Presbyterian - Brooklyn Methodist Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Morningside
state: New York
city: New York
country: United States
facility: Nyph/Cumc
state: New York
city: New York
country: United States
facility: Northwell Health (Lenox Hill)
state: New York
city: Poughkeepsie
country: United States
facility: Nuvance Health
state: New York
city: Staten Island
country: United States
facility: Northwell Health (Staten Island)
state: New York
city: Charlotte
country: United States
facility: Atrium Health Sanger Heart and Vascular Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Wilmington
country: United States
facility: Novant Health New Hanover Regional Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Cardiovascular Research Group
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Abington
country: United States
facility: Jefferson Abington Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Fort Worth
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: Texas Heart Institute
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White
state: Texas
city: Murray
country: United States
facility: Intermountain Health
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
References: