Protocolized Diuretic Strategy in Cardiorenal Failure
Condition: Cardiac Failure; Renal Failure; Kidney Failure
MeSH terms: Renal Insufficiency; Heart Failure
Intervention: Protocolized Diuretic Strategy
Intervention description: The Protocolized Diuretic Strategy will administer diuretics according to an algorithm based on based on the "stepped pharmacologic care arm" used by the CARRESS-HF trial investigators. This algorithm targets a relatively aggressive goal diuresis of urine output (UO) 3-5 L/day with diuretics intensified in a stepped fashion using both loop diuretics given by intravenous (IV) bolus followed by IV continuous infusion (furosemide or alternative loop diuretic at equivalent dose), with or without concomitant thiazide diuretic (oral (PO) metolazone or IV chlorothiazide).
Intervention MeSH terms: Diuretics
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 19.0
Sex: Male
Minimum age: 21 Years
Healthy volunteers: No
Keywords: Cardiorenal failure; Cardiorenal syndrome; Diuretic resistance; Volume overload; Edema; Health-related quality of life; Outcomes; Treatment protocol

Summary:

      This research study is a randomized clinical trial to evaluate if taking diuretics
      (medications that increase urine production and help with fluid removal from the body) in a
      standardized fashion (using a guideline for adjusting doses based on measured urine output)
      could improve health outcomes in patients with cardiorenal failure or cardiorenal syndrome
      (combined heart and kidney failure) with edema (too much fluid in their arms, legs, and/or
      lungs). Under usual care, these patients are treated with diuretics and other medications in
      increasing doses, but not necessarily to maintain a specific amount of urine output per day.
      Current heart failure (HF) treatment guidelines do not provide any standard protocol, or
      guideline, for adjusting diuretic doses. At the point when kidney function worsens to the
      degree that the kidneys are no longer able to respond to the medications used to remove
      fluid, either ultrafiltration (UF) or dialysis (also called hemodialysis [HD]) is typically
      started in order to remove fluid. In both UF and dialysis, excess fluid is removed from the
      body by using a machine. In dialysis, both waste products and fluid are removed and
      electrolyte abnormalities are corrected. In UF, only fluid is removed. Both procedures use
      the same machine. This study will test whether a Protocolized Diuretic Strategy (ProDiuS), a
      plan for adjusting diuretic doses based on measured urine output, will improve clinical care
      for cardiorenal syndrome. Such a plan for adjusting diuretic doses is needed to improve
      symptoms, decrease the length of hospital stays and rehospitalization rates, and improve
      health-related quality of life (HRQOL) in cardiorenal syndrome patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥21 years

          -  History of heart failure (HF), with either left ventricular (LV) dysfunction (EF<40%)
             or at least stage I diastolic or right ventricular (RV) dysfunction based on
             echocardiogram (ECHO) within the last year or diagnosis of HF by International
             Classification of Diseases (ICD-9)

          -  Evidence of renal dysfunction based on one of the following:

               -  Estimated glomerular filtration rate (GFR) 15-59 mL/min/1.73 m2 based on the
                  Modification of Diet in Renal Disease (MDRD) equation using serum creatinine (Cr)
                  obtained within 6 months of admission

               -  Elevated Cr above upper limits of normal

               -  An increase in serum Cr of ≥0.3 mg/dL or ≥50% from baseline on admission or
                  during diuretic therapy, with no alternative cause for worsening renal function,
                  while demonstrating signs and symptoms of persistent volume overload occurring
                  within 7 days before admission or during hospitalization

          -  Evidence of volume overload by clinical and/or radiographic features, with at least 2
             of the following: 1) peripheral edema ≥2+; 2) jugular venous distension ≥7 cm; 3)
             radiographic pulmonary edema or pleural effusion; 4) enlarged liver or ascites; 5)
             pulmonary rales, paroxysmal nocturnal dyspnea, or orthopnea; 6) elevated brain
             natriuretic peptide (BNP) level; 7) documentation of elevated right heart filling
             pressures by pulmonary artery catheter or right heart catheterization

        Exclusion Criteria:

          -  Use of inotropes (at time of screening)

          -  Acute indications for hemodialysis (HD) (e.g., severe hyperkalemia, metabolic
             acidosis, uremic signs or symptoms, pericardial friction rub)

          -  Specific forms of HF by chart diagnoses:

               1. Congenital heart disease

               2. Primary valvular heart disease due to severe valvular stenosis or acute severe
                  valvular regurgitation or valvular disease requiring immediate surgical repair

               3. Infiltrative cardiomyopathies

               4. Pulmonary hypertension (PH) as defined by World Health Organization (WHO) group I
                  and WHO group IV - Prior use of ultrafiltration (UF) or HD in the 3 months
                  preceding hospitalization

          -  End-stage renal disease (ESRD) requiring chronic dialysis or estimated GFR <15
             mL/min/1.73 m2 by MDRD equation (i.e., pre-existing ESRD)

          -  Prior cardiac or kidney transplantation

          -  Intravascular volume depletion based on clinical assessment

          -  Cardiogenic shock and/or systolic blood pressure (SBP) <90 mmHg

          -  Unstable coronary disease or acute coronary syndrome within 1 month of admission

          -  Alternative explanation for worsening renal function (e.g., obstructive nephropathy,
             contrast-induced nephropathy, acute tubular necrosis, intrinsic renal diseases)

          -  Life expectancy < 3 months due to other chronic health conditions (e.g., end-stage
             liver disease, pulmonary disease, malignancy, etc.)

          -  Psychiatric disorder requiring admission to a psychiatric hospital during HF admission

          -  Previous enrollment in this trial or other diuretic or UF trial in the prior 3 months

          -  Expected geographic unavailability for 3 months following hospital admission

          -  Pregnancy

          -  Inability to provide informed consent

          -  Physician's assessment that use of the protocol could be unsafe or lead to adverse
             consequences for the patient