Clinical trial NCT01474200: Study of Heart Failure Hospitalizations After Aquapheresis Therapy Compared to Intravenous (IV) Diuretic Treatment
Official title: Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Heart Failure
Cardiac Failure
Acute Decompensated Heart Failure (ADHF)
Keywords: Ultrafiltration
Aquapheresis
Diuretics
Loop Diuretics
Aquadex Flexflow System
Gambro UF Solutions
Lead sponsor: Nuwellis, Inc.
Sponsor class: INDUSTRY
First posted: 2011-11-18
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the research is to determine if patients have fewer Heart Failure (HF) events after receiving Aquapheresis (AQ) therapy compared to intravenous (IV) diuretics up to 90 days of discharge from the hospital. Heart Failure events are defined as returning to the hospital, clinic or emergency department (ED) for treatment of HF symptoms.

Detailed description: The aim of the proposed AVOID-HF study is to confirm and expand the findings that fluid removal by AQ reduces HF rehospitalizations at 90 days as well as the length of these HF rehospitalizations. In the "Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure" (UNLOAD) study, the 90 day HF re-hospitalizations were pre-specified secondary end-points. AVOID-HF is designed with a primary end-point to determine if AQ reduces the number of HF events (Rehospitalization or unscheduled outpatient or emergency room treatment for HF) after discharge from index hospitalization compared to IV loop diuretics. AVOID will also explore days alive and out of the hospital as a secondary end-point, which was not done in UNLOAD. In other words, the AVOID-HF study is going beyond studying only the amount of fluid removal and will explore whether the modality of fluid removal influences HF outcomes.

Eligibility criteria: Inclusion Criteria:

1. 18 years of age or older
2. Male or non-pregnant female patients
3. Admitted to the hospital with a primary diagnosis of acute decompensated heart failure (ADHF)
4. On regularly scheduled oral loop diuretics prior to admission
5. Fluid overload manifested by at least two of the following:

   1. Pitting edema (2+) of the lower extremities
   2. Jugular venous distention \> 8 cm
   3. Pulmonary edema or pleural effusion on chest x-ray
   4. Paroxysmal nocturnal dyspnea or ≥ two- pillow orthopnea
   5. Respiration rate ≥ 20 per minute.
6. Have received ≤ 2 IV loop diuretics doses before randomization
7. Must be able to be enrolled into the trial ≤ 24 hours of their admission to the hospital.
8. Provide written informed consent form as required by the local IRB (Institutional Review Board)

Exclusion Criteria:

1. Acute coronary syndromes
2. Renal insufficiency with a sCr ≥ 3.0 mg/dl or planned renal replacement therapies
3. Systolic blood pressure \< 90 mmHg at time of enrollment
4. Pulmonary Arterial Hypertension not secondary to left heart disease
5. Contraindications to systemic anticoagulation
6. Hematocrit \> 45%
7. Inability to obtain venous access
8. Hemodynamic instability severe enough to require IV positive inotropic agents, IV vasodilators or both
9. Use of iodinated radiocontrast material within the previous 72 hours or planned study requiring IV contrast during the current hospitalization
10. Severe concomitant disease expected to prolong hospitalization
11. Severe concomitant disease expected to cause death in ≤ 90 days
12. Sepsis or ongoing systemic infection
13. Severe uncorrected valvular stenosis
14. Active myocarditis
15. Hypertrophic obstructive cardiomyopathy
16. Constrictive pericarditis or restrictive cardiomyopathy
17. Liver cirrhosis
18. Previous solid organ transplant
19. Requirement for mechanical ventilatory support
20. Presence of a mechanical circulatory support device
21. Unwillingness or inability to complete follow up
22. Active drug or ETOH substance abuse
23. Participating in another interventional clinical trial

Primary outcomes:
measure: Time to First Heart Failure (HF) Event
timeFrame: 90 days after discharge from index HF hospitalization.
Secondary outcomes:
measure: EFFICACY: Total Fluid Removed During the Index Hospitalization
timeFrame: Index Hospitalization, an average of 8 days
measure: EFFICACY: Net Fluid Removed During the Index Hospitalization
timeFrame: Index Hospitalization, an average of 8 days
measure: EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment
timeFrame: 72 hours after treatment initiation
measure: EFFICACY: Total Weight Loss During the Index Hospitalization
timeFrame: Index Hospitalization, an average of 8 days
measure: EFFICACY: Time to Freedom From Congestion
timeFrame: Index Hospitalization, an average of 8 days
measure: EFFICACY: Freedom From Congestion
timeFrame: Index Hospitalization, an average of 8 days
measure: EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time
timeFrame: Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge
measure: Length of Stay (LOS) During the Index Hospitalization
timeFrame: Index hospitalization admission to index hospitalization discharge
measure: CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge
timeFrame: Within 30 days and 90 days after hospital discharge
measure: CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge
timeFrame: Within 30 days and 90 days after hospital discharge
measure: CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge
timeFrame: Within 30 days and 90 days after hospital discharge
measure: CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge
timeFrame: Within 30 days and 90 days after hospital discharge
measure: CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge
timeFrame: Within 30 days and 90 days after hospital discharge
measure: CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days
timeFrame: Within 30 days and 90 days after hospital discharge
measure: Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge.
timeFrame: Time from randomization to 90 days post-hospital discharge
measure: Days Alive and Out of Hospital at 30 and 90 Days After Discharge
timeFrame: Within 30 and 90 days after hospital discharge
measure: Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge
timeFrame: Within 90 days after hospital discharge
measure: CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge
timeFrame: Within 90 days after hospital discharge
measure: SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization
timeFrame: Within 90 days of randomization
measure: SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization
timeFrame: Within 90 days of randomization
measure: SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization
timeFrame: Within 90 days of randomization
measure: SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization
timeFrame: Within 90 days of randomization
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Heart Center Research
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: San Diego
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: San Diego
country: United States
facility: San Diego Cardiac Center
state: California
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital Center for Advanced Heart Failure
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Advocate Health & Hospitals Corporation
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General HealthCare
state: Indiana
city: Fort Wayne
country: United States
facility: Northern Indiana Research Alliance
state: Indiana
city: Des Moines
country: United States
facility: Iowa Health - Des Moines
state: Iowa
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis VA Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Hospital and Saint Luke's Cardiovascular Consultants
state: Missouri
city: Egg Harbor Township
country: United States
facility: AtlantiCare Health Network
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute/Heart Hospital
state: New Mexico
city: Asheville
country: United States
facility: Asheville Cardiology Associates
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Systems
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital - Dayton
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute and Hillcrest Medical Center
state: Oklahoma
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Saint Thomas Hospital
state: Tennessee
city: San Antonio
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Health System/Tacoma General Hospital
state: Washington
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
Study officials:
affiliation: Midwest Heart Foundation
name: Maria Rosa Costanzo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, Jaski BE, Fang JC, Feller ED, Haas GJ, Anderson AS, Schollmeyer MP, Sobotka PA; UNLOAD Trial Investigators. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007 Feb 13;49(6):675-83. doi: 10.1016/j.jacc.2006.07.073. Epub 2007 Jan 26.
citation: Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, Berkowitz RL, Galvao M, Horton DP; ADHERE Scientific Advisory Committee and Investigators. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005 Feb;149(2):209-16. doi: 10.1016/j.ahj.2004.08.005.
citation: Jain P, Massie BM, Gattis WA, Klein L, Gheorghiade M. Current medical treatment for the exacerbation of chronic heart failure resulting in hospitalization. Am Heart J. 2003 Feb;145(2 Suppl):S3-17. doi: 10.1067/mhj.2003.149. No abstract available.
citation: Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med. 2001 Aug 23;345(8):574-81. doi: 10.1056/NEJMoa010641.
citation: Domanski M, Norman J, Pitt B, Haigney M, Hanlon S, Peyster E; Studies of Left Ventricular Dysfunction. Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 2003 Aug 20;42(4):705-8. doi: 10.1016/s0735-1097(03)00765-4.
citation: Sharma A, Hermann DD, Mehta RL. Clinical benefit and approach of ultrafiltration in acute heart failure. Cardiology. 2001;96(3-4):144-54. doi: 10.1159/000047398.
citation: Marenzi G, Lauri G, Grazi M, Assanelli E, Campodonico J, Agostoni P. Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure. J Am Coll Cardiol. 2001 Oct;38(4):963-8. doi: 10.1016/s0735-1097(01)01479-6.
citation: Rimondini A, Cipolla CM, Della Bella P, Grazi S, Sisillo E, Susini G, Guazzi MD. Hemofiltration as short-term treatment for refractory congestive heart failure. Am J Med. 1987 Jul;83(1):43-8. doi: 10.1016/0002-9343(87)90495-5.
citation: Jaski BE, Ha J, Denys BG, Lamba S, Trupp RJ, Abraham WT. Peripherally inserted veno-venous ultrafiltration for rapid treatment of volume overloaded patients. J Card Fail. 2003 Jun;9(3):227-31. doi: 10.1054/jcaf.2003.28.
citation: Bart BA, Boyle A, Bank AJ, Anand I, Olivari MT, Kraemer M, Mackedanz S, Sobotka PA, Schollmeyer M, Goldsmith SR. Ultrafiltration versus usual care for hospitalized patients with heart failure: the Relief for Acutely Fluid-Overloaded Patients With Decompensated Congestive Heart Failure (RAPID-CHF) trial. J Am Coll Cardiol. 2005 Dec 6;46(11):2043-6. doi: 10.1016/j.jacc.2005.05.098. Epub 2005 Nov 4.
citation: Costanzo MR, Saltzberg M, O'Sullivan J, Sobotka P. Early ultrafiltration in patients with decompensated heart failure and diuretic resistance. J Am Coll Cardiol. 2005 Dec 6;46(11):2047-51. doi: 10.1016/j.jacc.2005.05.099. Epub 2005 Nov 9.
citation: Bart BA, Goldsmith SR, Lee KL, Givertz MM, O'Connor CM, Bull DA, Redfield MM, Deswal A, Rouleau JL, LeWinter MM, Ofili EO, Stevenson LW, Semigran MJ, Felker GM, Chen HH, Hernandez AF, Anstrom KJ, McNulty SE, Velazquez EJ, Ibarra JC, Mascette AM, Braunwald E; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012 Dec 13;367(24):2296-304. doi: 10.1056/NEJMoa1210357. Epub 2012 Nov 6.