Study of Heart Failure Hospitalizations After Aquapheresis Therapy Compared to Intravenous (IV) Diuretic Treatment (AVOID-HF)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Heart Failure; Cardiac Failure; Acute Decompensated Heart Failure (ADHF)	Device: Isolated veno-venous ultrafiltration (AQ); Drug: IV Loop Diuretics (LD)	Not Applicable

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	224 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)
Study Start Date :	January 2012
Actual Primary Completion Date :	July 2014
Actual Study Completion Date :	July 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Aquapheresis (AQ) - isolated veno-venous ultrafiltration; Excess fluid from the patient is removed by isolated veno-venous ultrafiltration treatment using the Aquadex Flex Flow System	Device: Isolated veno-venous ultrafiltration (AQ); Aquapheresis treatment (isolated veno-venous ultrafiltration) using the Aquadex FlexFlow System during index hospitalization until the patient's signs and symptoms of fluid overload have improved to the satisfaction of the treating physician. Ultrafiltration rates, duration and frequency of treatment are dependent on the amount of patient fluid excess and on the rate of fluid movement from the interstitial spaces into the vascular compartment during Aquapheresis (Plasma Refill Rate, or PRR); Other Names: Aquapheresis; Ultrafiltration; Aquadex FlexFlow System; Gambro UF Solutions
Active Comparator: IV Loop Diuretics (LD); Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment	Drug: IV Loop Diuretics (LD); IV Loop Diuretics treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload. This includes furosemide or other IV loop diuretics administered at equivalent doses to furosemide. Patients will receive either a twice daily IV bolus or continuous IV LD infusions according to the high dose protocol of the"Diuretic strategies in patients wth acute decompensated heart failure" (DOSE) trial.; Other Name: furosemide

Outcome Measures

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Primary Outcome Measures :

1. Time to First Heart Failure (HF) Event [ Time Frame: 90 days after discharge from index HF hospitalization. ]

   Time to first HF event within 90 days after discharge from index HF hospitalization. HF events are defined as

   • HF rehospitalization or
   • unscheduled outpatient or emergency room treatment with IV loop diuretics or
   • unscheduled outpatient Aquapheresis treatment

Secondary Outcome Measures :

1. EFFICACY: Total Fluid Removed During the Index Hospitalization [ Time Frame: Index Hospitalization, an average of 8 days ]
   AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics
2. EFFICACY: Net Fluid Removed During the Index Hospitalization [ Time Frame: Index Hospitalization, an average of 8 days ]
   AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.
3. EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment [ Time Frame: 72 hours after treatment initiation ]
   Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.
4. EFFICACY: Total Weight Loss During the Index Hospitalization [ Time Frame: Index Hospitalization, an average of 8 days ]
   Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.
5. EFFICACY: Time to Freedom From Congestion [ Time Frame: Index Hospitalization, an average of 8 days ]
   Time from hospital admission to time patient is free of congestion in the hospital. Freedom from congestion is defined as jugular venous distention of < or equal to 8 cm, with no orthopnea and with trace peripheral edema or no edema. Measurement taken every 24 hours after treatment initiation.
6. EFFICACY: Freedom From Congestion [ Time Frame: Index Hospitalization, an average of 8 days ]
   Defined as jugular venous distention of < or equal to 8 cm, with no orthopnea, and with trace peripheral edema or no edema at hospital discharge
7. EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time [ Time Frame: Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge ]
   Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.
8. CLINICAL: Length of Stay (LOS) During the Index Hospitalization [ Time Frame: Index hospitalization admission to index hospitalization discharge ]
   Number of days patient is in hospital for HF treatment.
9. CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge [ Time Frame: Within 30 days and 90 days after hospital discharge ]
   Days rehospitalized for HF symptoms requiring hospital, emergency room or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs.
10. CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge [ Time Frame: Within 30 days and 90 days after hospital discharge ]
    Number of visits for HF symptoms requiring ED or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs
11. CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge [ Time Frame: Within 30 days and 90 days after hospital discharge ]
    Number of different times patient was admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.
12. CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge [ Time Frame: Within 30 days and 90 days after hospital discharge ]
    CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.
13. CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge [ Time Frame: Within 30 days and 90 days after hospital discharge ]
    The total number of days spent in the hospital due to CV related events at 30 days and 90 days from hospital discharge.
14. CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days [ Time Frame: Within 30 days and 90 days after hospital discharge ]
    Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.
15. CLINICAL: Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge. [ Time Frame: Time from randomization to 90 days post-hospital discharge ]
    Death due to any cause.
16. CLINICAL: Days Alive and Out of Hospital at 30 and 90 Days After Discharge [ Time Frame: Within 30 and 90 days after hospital discharge ]
    Number of days patients were alive and out of the hospital.
17. CLINICAL: Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge [ Time Frame: Within 90 days after hospital discharge ]
    Questionnaire assessed patients quality of life prior to index treatment versus timeframes following hospital discharge. Scores were transformed to a range of 0-100, in which higher scores reflect better health status.
18. CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge [ Time Frame: Within 90 days after hospital discharge ]
    KCCQ Questionnaire analysis based on patient's self-assessment of how they feel at various intervals compared to how they felt prior to index treatment. Scores were transformed to a range of 0-100, in which higher scores reflect better health status.
19. SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization [ Time Frame: Within 90 days of randomization ]
    Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula
20. SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization [ Time Frame: Within 90 days of randomization ]
    Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula
21. SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization [ Time Frame: Within 90 days of randomization ]
    Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula
22. SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization [ Time Frame: Within 90 days of randomization ]
    Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 38 Study Locations

Sponsors and Collaborators

Baxter Healthcare Corporation

Gambro UF Solutions, Inc.

Gambro Renal Products, Inc.

Investigators

Principal Investigator:	Maria Rosa Costanzo, MD	Midwest Heart Foundation

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

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. Epub 2007 Jan 26. Erratum in: J Am Coll Cardiol. 2007 Mar 13;49(10):1136.

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.

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. Review.

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.

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.

Sharma A, Hermann DD, Mehta RL. Clinical benefit and approach of ultrafiltration in acute heart failure. Cardiology. 2001;96(3-4):144-54. Review.

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.

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.

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.

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. Epub 2005 Nov 4.

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. Epub 2005 Nov 9.

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.

Responsible Party:	Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:	NCT01474200 History of Changes
Other Study ID Numbers:	Gambro 1494
First Posted:	November 18, 2011
Results First Posted:	October 12, 2015
Last Update Posted:	May 10, 2017
Last Verified:	April 2017

Keywords provided by Baxter Healthcare Corporation:

Ultrafiltration; Aquapheresis; Diuretics	Loop Diuretics; Aquadex Flexflow System; Gambro UF Solutions

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases; Furosemide; Diuretics	Sodium Potassium Chloride Symporter Inhibitors; Natriuretic Agents; Physiological Effects of Drugs; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action