Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure (TACTICS-HF)

• Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours [ Time Frame: 8 and 24 hours ]
  The number of patients with at least moderate improvement (as reported by patient) in dyspnea Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.
  
  

• Renal Function [ Time Frame: 0, 24, 48 and 72 hours ]
  Change in Serum creatinine from baseline to 24, 48 and 72 hours
  
  
• Weight Loss [ Time Frame: 0, 24, 48, and 72 hours ]
  Change in body weight from baseline to 24, 48, and 72 hours
  
  
• Fluid Loss [ Time Frame: 0, 24, 48, and 72 hours ]
  Change from baseline fluid balance at 24, 48, and 72 hours
  
  
• Dyspnea Likert [ Time Frame: 48 and 72 hours ]
  Number of patients that experience moderate or greater improvement (patient reported) in dyspnea by 7 point Likert scale at 48 and 72 hours
  
  
• Hospital Stay [ Time Frame: 7 days ]
  Total days spent in hospital from baseline until discharge or death
  
  
• Worsening or Persistent Heart Failure or Death [ Time Frame: 72 hrs ]
  Number of patients with worsening heart failure or death
  
  
• Over-diuresis [ Time Frame: 72 hours ]
  clinical evidence of volume depletion requiring intervention other than holding diuretics during the 72 hours after randomization
  
  
• Serum Sodium [ Time Frame: 0, 24, 48, and 72 hours ]
  Change in serum sodium from baseline to 24, 48, and 72 hours
  
  
• Dyspnea 11 Point NRS [ Time Frame: 0, 24, 48, and 72 hours ]
  Change in NRS for assessment of dyspnea from baseline to 24, 48, and 72 hours (scale ranges from 0-No difficulty breathing to 10-Difficulty as bad as you can imagine)
  
  
• Freedom From Congestion [ Time Frame: 24, 48, and 72 hours ]
  Jugular Venous Pressure (JVP) < 8 cm, no orthopnea, trace peripheral edema or less, and will be assessed at 24, 48, and 72 hours
  
  
• Development of Worsening Renal Function [ Time Frame: 72 hours ]
  increase in serum creatinine ≥ 0.3mg/dl from randomization at any time point during 72 hours after randomization
  
  
• Days Hospitalized or Deceased [ Time Frame: 30 days ]
  Total days hospitalized or deceased during the 30 days after randomization
  
  
• All Cause Death or Rehospitalization [ Time Frame: 30 days ]
  All cause death or rehospitalization (to include unscheduled clinic visits or ED visits) at 30 days (Kaplan-Meier and 95% confidence interval)
  
  

This study will be a randomized, double blind, placebo controlled, multi-center clinical trial of patients with signs and symptoms consistent with AHF within 24 hours of presentation at Emergency Department. A total of approximately 250 patients will be enrolled in the trial.

Patients will be randomized in a 1:1 ratio to either of 2 treatment regimens:

• Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours)
• Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 24 and 48 hours)

The study treatment regimen will be administered from randomization through 48 hours, at which point Tolvaptan/placebo will be discontinued and all diuretic treatment will be adjusted at the treating physician's discretion.

The primary endpoint will be the proportion of patients with at least moderate improvement in dyspnea by Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.

Patients will be followed daily for the duration of hospitalization or for 7 days (whichever is shortest).

All patients will have Day 30 follow up phone contact for assessment of vital status and interval hospitalizations.