Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure
Condition: Heart Failure; Dyspnea
MeSH terms: Dyspnea; Heart Failure
Intervention: Tolvaptan; Placebo
Intervention description: IV furosemide plusTolvaptan (given at 0, 24 and 48 hours); IV furosemide plus oral placebo (given at 0, 24 and 48 hours)
Intervention MeSH terms: Tolvaptan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 257.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to compare the effects of oral Tolvaptan vs. placebo
      as an adjunct to fixed dose IV furosemide on dyspnea relief in patients with acute
      decompensated heart failure

      The primary hypothesis is that the addition of oral Tolvaptan to fixed dose furosemide will
      be more effective at relieving dyspnea than fixed dose furosemide alone
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 18 years of age

          -  Daily oral dose of furosemide between ≥ 40 mg(or equivalent)

          -  Identified within 24 hours of presentation, defined for purposes of this study as the
             time of initial dose of intravenous loop diuretic

          -  Prior clinical HF diagnosis that was treated with oral loop diuretics for at least 1
             month

          -  Admission for acute decompensated Heart Failure (HF) as determined by

               -  dyspnea at rest or with minimal exertion

               -  Brain Natriuretic Peptide (BNP) > 400 or NTproBNP > 2000 pg/mL

        AND at least one of the following additional signs and symptoms:

          -  Orthopnea

          -  Peripheral edema

          -  Elevated JVP (Jugular Venous Pressure)

          -  Pulmonary rales

          -  Congestion on Chest X-ray

          -  No plan for revascularization, cardiac transplant, of ventricular assist device
             implantation, or other cardiac surgery within 60 days of randomization

          -  Signed informed consent

        Exclusion Criteria:

          -  Serum Na > 140 meq/L

          -  Received IV vasoactive treatment or ultra-filtration therapy for HF since initial
             presentation

          -  Treatment plan during current hospitalization includes IV vasoactive treatment or
             ultra-filtration for HF

          -  Systolic Blood Pressure (SBP)<90mmHg

          -  Serum-Cr>3.5mg/dl or currently undergoing renal replacement therapy

             . Known underlying liver disease

          -  Hemodynamically significant arrhythmias

          -  ACS(Acute coronary syndrome) within 4 weeks prior to study entry

          -  Active myocarditis

          -  Hypertrophic obstructive, restrictive, constrictive cardiomyopathy

          -  Severe stenotic valvular disease

          -  Complex congenital heart disease

          -  Constrictive pericarditis

          -  Clinical evidence of digoxin toxicity

          -  Need for mechanical hemodynamic support

          -  Terminal illness (other than heart failure) with expected survival time of less than 1
             year

          -  History of adverse reaction to Tolvaptan

          -  Enrollment or planned enrollment in another randomized clinical trial during this
             hospitalization

          -  Pregnant or breast-feeding

          -  Inability to comply with planned study procedures