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

Heart Failure Clinical Trial

— AVOID-HF  

Official title:

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01474200
• Other study ID #: 1494
• Status: Terminated
• Phase: N/A
• Start date: January 2012
• Est. completion date: July 2014

Study information

• Verified date: August 2023
• Source: Nuwellis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 224
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure (ADHF)
• Cardiac Failure
• Heart Failure

Intervention

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)

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.

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	New Mexico Heart Institute/Heart Hospital	Albuquerque	New Mexico
United States	Asheville Cardiology Associates	Asheville	North Carolina
United States	Emory University	Atlanta	Georgia
United States	St. Luke's Hospital and Health Network	Bethlehem	Pennsylvania
United States	University of Cincinnati	Cincinnati	Ohio
United States	Morton Plant Medical Center	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	MetroHealth Systems	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Iowa Health - Des Moines	Des Moines	Iowa
United States	AtlantiCare Health Network	Egg Harbor Township	New Jersey
United States	Elkhart General HealthCare	Elkhart	Indiana
United States	Northwestern University	Evanston	Illinois
United States	Northern Indiana Research Alliance	Fort Wayne	Indiana
United States	Heart Center Research	Huntsville	Alabama
United States	Saint Luke's Hospital and Saint Luke's Cardiovascular Consultants	Kansas City	Missouri
United States	UCLA	Los Angeles	California
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	Edward Hospital Center for Advanced Heart Failure	Naperville	Illinois
United States	Saint Thomas Hospital	Nashville	Tennessee
United States	Advocate Health & Hospitals Corporation	Oakbrook Terrace	Illinois
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University Medical Center	Richmond	Virginia
United States	Brooke Army Medical Center	San Antonio	Texas
United States	San Diego Cardiac Center	San Diego	California
United States	University of California, San Diego (UCSD)	San Diego	California
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	Scottsdale Healthcare Research Institute	Scottsdale	Arizona
United States	MultiCare Health System/Tacoma General Hospital	Tacoma	Washington
United States	Oklahoma Heart Institute and Hillcrest Medical Center	Tulsa	Oklahoma
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Nuwellis, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View 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. — View 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. — View 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. Erratum In: J Am Coll Cardiol. 2007 Mar 13;49(10):1136. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to First Heart Failure (HF) Event	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	90 days after discharge from index HF hospitalization.
Secondary	EFFICACY: Total Fluid Removed During the Index Hospitalization	AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics	Index Hospitalization, an average of 8 days
Secondary	EFFICACY: Net Fluid Removed During the Index Hospitalization	AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.	Index Hospitalization, an average of 8 days
Secondary	EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment	Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.	72 hours after treatment initiation
Secondary	EFFICACY: Total Weight Loss During the Index Hospitalization	Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.	Index Hospitalization, an average of 8 days
Secondary	EFFICACY: Time to Freedom From Congestion	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.	Index Hospitalization, an average of 8 days
Secondary	EFFICACY: Freedom From Congestion	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	Index Hospitalization, an average of 8 days
Secondary	EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time	Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.	Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge
Secondary	Length of Stay (LOS) During the Index Hospitalization	Number of days patient is in hospital for HF treatment.	Index hospitalization admission to index hospitalization discharge
Secondary	CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After 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.	Within 30 days and 90 days after hospital discharge
Secondary	CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After 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	Within 30 days and 90 days after hospital discharge
Secondary	CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge	Number of different times patient was admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.	Within 30 days and 90 days after hospital discharge
Secondary	CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge	CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.	Within 30 days and 90 days after hospital discharge
Secondary	CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge	The total number of days spent in the hospital due to CV related events at 30 days and 90 days from hospital discharge.	Within 30 days and 90 days after hospital discharge
Secondary	CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days	Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.	Within 30 days and 90 days after hospital discharge
Secondary	Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge.	Death due to any cause within index hospitalization and 90 days following hospital discharge.	Time from randomization to 90 days post-hospital discharge
Secondary	Days Alive and Out of Hospital at 30 and 90 Days After Discharge	Number of days patients were alive and out of the hospital at 30 and 90 days after discharge.	Within 30 and 90 days after hospital discharge
Secondary	Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After 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.	Within 90 days after hospital discharge
Secondary	CLINICAL: Global Clinical Score at 30 and 90 Days After 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.	Within 90 days after hospital discharge
Secondary	SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After 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	Within 90 days of randomization
Secondary	SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After 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	Within 90 days of randomization
Secondary	SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After 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	Within 90 days of randomization
Secondary	SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After 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	Within 90 days of randomization