Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure
Heart Failure
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring loop diuretics, thiazide diuretics, vasopressin antagonists, diuretic resistance, heart failure
Eligibility Criteria
Inclusion Criteria:
- age of 18 years or older
- hospital admission for hypervolemic decompensated heart failure complicated by loop diuretic resistance
- 24 hour telemetry monitoring on an inpatient ward
- basic metabolic panel laboratory assessment twice daily during the study period
Hypervolemia will be diagnosed by the admitting provider as either (i) pulmonary artery catheterization with a pulmonary capillary wedge pressure greater than 19mmHg plus a systemic physical exam finding of hypervolemia (peripheral edema, ascites, or pulmonary edema on auscultation) or (ii) in the absence of pulmonary artery catheterization data 2 of the following signs or symptoms: peripheral edema ascites, jugular venous pressure > 10mmHg, or pulmonary edema on chest x-ray.
Loop diuretic resistance is defined as a provider decision to pursue combination diuretic therapy because of failure to reach provider defined adequate diuresis (can not exceed urine output of 2 L in past 12 hours) despite receipt of an intravenous loop diuretic dose of a furosemide equivalent of at least 240mg/day over at least the past 12 hours (40mg furosemide = 20mg torsemide = 1mg bumetanide).
Exclusion Criteria:
- decision to pursue hemodialysis by a nephrologist
- estimated glomerular filtration rate by the MDRD equation < 15ml/min/m2
- systolic blood pressure < 85mmHg
- pregnancy
- serum potassium < 3.0mEq/L
- serum sodium > 145mEq/L or < 130mEq/L
- severe malnutrition
- advanced liver disease
- inability to perform standing weights
- inability to collect and measure urine with either a foley catheter or urine collection containers
- concomitant therapy with strong CYP3A4 inhibitors/inducers (systemic ketoconazole, clarithromycin, itraconazole, telithromycin, saquinavir, nelfinavir, ritonavir, nefazodone, rifampin, rifabutin, rifapentine, phenytoin, phenobarbital, carbamazepine, St. John's Wort)
- concomitant therapy with p-glycoprotein inhibitors (cyclosporine, erythromycin, tacrolimus, dronedarone, quinidine, or verapamil)
- non-study diuretics (spironolactone doses >75mg/day, eplerenone > 75mg/day, non-study thiazides or loop diuretics, or systemic acetazolamide, triamterene, or amiloride therapy)
- thiazides administration in the previous 24 hours prior to randomization
Sites / Locations
- Vanderbilt University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Active Comparator
Experimental
Experimental
Metolazone
Chlorothiazide
Tolvaptan
Metolazone 5mg tablet orally twice daily for 48 hours.
Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours
Tolvaptan 30mg tablet orally once daily for 48 hours