Broad Objectives: To determine the comparative efficacy of commonly employed strategies to overcome loop diuretic resistance when added to concomitant loop diuretics in hospitalized decompensated heart failure patients with hypervolemia Specific Aims: 1. Compare the 48-hour weight change of either intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in decompensated heart failure 2. Compare the adverse effects of electrolyte depletion and renal function changes between intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure 3. Pharmacoeconomic analysis of the direct costs of intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure The investigators will conduct a dual center, randomized, double-blind, double-dummy, parallel design trial comparing: oral metolazone, intravenous chlorothiazide, or oral tolvaptan, in combination with loop diuretics in 60 patients hospitalized for hypervolemic decompensated heart failure and displaying loop diuretic resistance.
Name: tolvaptan
Name: Chlorothiazide
Name: Metolazone
Description: The primary outcome will be 48-hour standing scale weight change (kg) from enrollment among the metolazone, intravenous chlorothiazide, and tolvaptan arms, using metolazone group as the comparator group for all other groups.
Measure: Weight Change Over 48 Hours Time: 48 hoursDescription: Net urine output from enrollment to the end of study at 48 hours measured in liters
Measure: Net Urine Output Time: 48 hoursDescription: Mean change in serum creatinine (mg/dl) from enrollment to end of study at 48 hours
Measure: Mean Change in Serum Creatinine Time: 48 hoursDescription: Mean change in glomerular filtration rate from enrollment to end of study at hospital discharge, an average of 5 days
Measure: Mean Change in Glomerular Filtration Rate at Discharge Time: hospital discharge an average of 5 daysDescription: Mean change in serum potassium (mEq/L) from enrollment to end of study at 48 hours
Measure: Mean Change in Serum Potassium Time: 48 hoursDescription: Cumulative dose of potassium supplementation (mEq) administered from enrollment to end of study at 48 hours
Measure: Potassium Supplementation Time: 48 hoursDescription: Incidence of hypokalemia (serum potassium less than 3.5mEq/L ) from enrollment to end of study
Measure: Number of Patients With Hypokalemia Time: 48 hoursDescription: Provider escalation of loop diuretic dosage at 24 hours for urine output less than 3 L at 24 hours
Measure: Number of Patients With Escalation of Loop Diuretic Therapy Time: 24 hoursDescription: Incidence of new atrial or ventricular arrhythmias from enrollment to end of study at 48 hours
Measure: Number of Patients With Cardiac Arrhythmias Time: 48 hoursDescription: SBP < 85 mmHg plus medical intervention for symptomatic hypotension
Measure: Number of Patients With Symptomatic Hypotension Time: 48 hoursDescription: Change in estimated glomerular filtration rate (ml/min/m2) from baseline to 48 hours
Measure: Change in eGFR From Baseline to 48 Hours Time: 48 hoursDescription: Mean change in serum sodium (mEq/L) from enrollment to end of study at 48 hours
Measure: Mean Change in Serum Sodium Time: 48 hoursDescription: Incidence of death from study enrollment to hospital discharge, an average of 5 days
Measure: Number of Patients With In-hospital Mortality Time: Enrollment to hospital discharge an average of 5 daysDescription: Incidence of new initiation of dopamine, dobutamine, or milrinone from enrollment to end of study at 48 hours
Measure: Number of Patients With New Inotrope Utilization Time: 48 hoursDescription: Incidence of Renal replacement therapy utilization (hemodialysis, ultrafiltration) from enrollment to hospital discharge, an average of 5 days
Measure: Number of Patients With Renal Replacement Therapy Utilization Time: enrollment to hospital discharge an average of 5 daysDescription: Diuretic Efficiency is calculated as 48hr urine output/ 48hr Furosemide equivalents in milligrams
Measure: Diuretic Efficiency Time: 48 hoursDescription: Change in serum chloride (mEq/L) from baseline to 48 hrs
Measure: Change in Serum Chloride From Baseline Time: 48 hoursDescription: Participants will score their congestion on a 10cm scale ranging from "Best" (10cm) to "Worst" (0cm). Change in score (units in centimeters) from baseline to 48 hours.
Measure: Change in Patient Congestion Score Time: 48 hoursAllocation: Randomized
Parallel Assignment
There is one SNP
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H ---
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H ---
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H ---
Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H --- --- Q12H ---