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

This study has been terminated.
(Closed due to patient recruitment challenges. No interim analyses were completed; study closure was not related to any concerns about safety or futility.)
Sponsor:
Collaborator:
Gambro UF Solutions, Inc.
Information provided by (Responsible Party):
Gambro Renal Products, Inc.
ClinicalTrials.gov Identifier:
NCT01474200
First received: November 11, 2011
Last updated: April 14, 2014
Last verified: April 2014

November 11, 2011
April 14, 2014
January 2012
May 2016   (final data collection date for primary outcome measure)
Time to first HF event [ Time Frame: 90 days after discharge from index HF hospitalization. ] [ Designated as safety issue: No ]

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
Time to first HF event [ Time Frame: 90 days after discharge from index HF hospitalization. ] [ Designated as safety issue: No ]
Time to first HF event (Rehospitalization or unscheduled outpatient or emergency room treatment for HF) within 90 days after discharge from index HF hospitalization.
Complete list of historical versions of study NCT01474200 on ClinicalTrials.gov Archive Site
  • EFFICACY: Total fluid removed during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics
  • EFFICACY: Net fluid removed during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.
  • EFFICACY: Weight loss at 72 hours after initiation of treatment [ Time Frame: 72 hours after treatment initiation ] [ Designated as safety issue: No ]
    Weight at 72 hours after treatment initiation minus weight at treatment initiation.
  • EFFICACY: Total weight loss during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    Weight at hospital discharge minus weight at hospital admission
  • EFFICACY: Time to freedom from congestion [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    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.
  • EFFICACY: Freedom from congestion [ Time Frame: Participants will be followed for the duration of index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    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
  • EFFICACY: Changes in B-type natriuretic peptide (BNP) levels over time [ Time Frame: At 72 hours from baseline, at hospital discharge, at 30 days, 60 days and 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Blood tests to determine level of BNP at prescribed intervals.
  • CLINICAL: Length of stay (LOS) during the index hospitalization [ Time Frame: Duration from index hospitalization admission to index hospitalization discharge, an expected average of 6 days ] [ Designated as safety issue: No ]
    Number of days patient is in hospital for HF treatment.
  • CLINICAL: Total number of days rehospitalized for Heart Failure (HF) at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    HF symptoms requiring hospital, emergency room or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs.
  • CLINICAL: Total number of Emergency Department (ED) or unscheduled office visits at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    HF symptoms requiring hospital, ED or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs
  • CLINICAL: Total number of Heart Failure (HF) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Number of different times patient iS admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.
  • CLINICAL: Total number of cardiovascular (CV) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    CV symptoms that require hospitalization for treatment within 90 days of index hospitalization discharge.
  • CLINICAL: Total number of days for cardiovascular (CV) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  • CLINICAL: All cause rehospitalization rates at 30 and 90 days [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Any cause that requires hospitalization for treatment within 90 days of index hospitalization discharge.
  • CLINICAL: Mortality rates within index hospitalization or within 90 days after hospital discharge. [ Time Frame: Time from randomization to 90 days post-hospital discharge ] [ Designated as safety issue: No ]
    Death due to any cause.
  • CLINICAL: Days alive and out of hospital at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Death due to any cause post-hospital discharge.
  • 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 ] [ Designated as safety issue: No ]
    Questionnaire assessing patients quality of life prior to index treatment versus timeframes following hospital discharge.
  • CLINICAL: Global clinical score at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Patient's self assessment of how they feel at various intervals compared to how they felt prior to index treatment.
  • SAFETY: Changes in renal function variables after treatment up to 90 days after randomization [ Time Frame: Within 90 days of randomization ] [ Designated as safety issue: Yes ]
    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
  • EFFICACY: Total fluid removed during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics
  • EFFICACY: Net fluid removed during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.
  • EFFICACY: Weight loss at 72 hours after initiation of treatment [ Time Frame: 72 hours after treatment initiation ] [ Designated as safety issue: No ]
    Weight at 72 hours after treatment initiation minus weight at treatment initiation.
  • EFFICACY: Total weight loss during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    Weight at hospital discharge minus weight at hospital admission
  • EFFICACY: Time to freedom from congestion [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    Time from hospital admission to time patient is free of congestion in the hospital. Freedom from congestion is defined as jugular venous pressure 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.
  • EFFICACY: Freedom from congestion [ Time Frame: Participants will be followed for the duration of index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
    Defined as jugular venous pressure of < or equal to 8 cm, with no orthopnea, and with trace peripheral edema or no edema at hospital discharge
  • EFFICACY: Changes in B-type natriuretic peptide (BNP) levels over time [ Time Frame: At 72 hours from baseline, at hospital discharge, at 30 days, 60 days and 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Blood tests to determine level of BNP at prescribed intervals.
  • CLINICAL: Length of stay (LOS) during the index hospitalization [ Time Frame: Duration from index hospitalization admission to index hospitalization discharge, an expected average of 6 days ] [ Designated as safety issue: No ]
    Number of days patient is in hospital for HF treatment.
  • CLINICAL: Total number of days rehospitalized for Heart Failure (HF) at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    HF symptoms requiring hospital, emergency room or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs.
  • CLINICAL: Total number of Emergency Department (ED) or unscheduled office visits at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    HF symptoms requiring hospital, ED or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs
  • CLINICAL: Total number of Heart Failure (HF) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Number of different times patient iS admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.
  • CLINICAL: Total number of cardiovascular (CV) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    CV symptoms that require hospitalization for treatment within 90 days of index hospitalization discharge.
  • CLINICAL: Total number of days for cardiovascular (CV) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  • CLINICAL: All cause rehospitalization rates at 30 and 90 days [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Any cause that requires hospitalization for treatment within 90 days of index hospitalization discharge.
  • CLINICAL: Mortality rates within index hospitalization or within 90 days after hospital discharge. [ Time Frame: Time from randomization to 90 days post-hospital discharge ] [ Designated as safety issue: No ]
    Death due to any cause.
  • CLINICAL: Days alive and out of hospital at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Death due to any cause post-hospital discharge.
  • CLINICAL: Quality of life assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Questionnaire assessing patients quality of life prior to index treatment versus timeframes following hospital discharge.
  • CLINICAL: Global clinical score at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
    Patient's self assessment of how they feel at various intervals compared to how they felt prior to index treatment.
  • SAFETY: Changes in renal function variables after treatment up to 90 days after randomization [ Time Frame: Within 90 days of randomization ] [ Designated as safety issue: Yes ]
    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
Not Provided
Not Provided
 
Study of Heart Failure Hospitalizations After Aquapheresis Therapy Compared to Intravenous (IV) Diuretic Treatment
Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Heart Failure
  • Cardiac Failure
  • Acute Decompensated Heart Failure (ADHF)
  • 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
  • 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
  • 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
    Intervention: Device: Isolated veno-venous ultrafiltration (AQ)
  • Active Comparator: IV Loop Diuretics (LD)
    Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment
    Intervention: Drug: IV Loop Diuretics (LD)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
224
May 2016
May 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01474200
Gambro 1494
Yes
Gambro Renal Products, Inc.
Gambro Renal Products, Inc.
Gambro UF Solutions, Inc.
Principal Investigator: Maria Rosa Costanzo, MD Midwest Heart Foundation
Gambro Renal Products, Inc.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP