Aquaresis Utility for Hyponatremic Acute Heart Failure Study
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: Tolvaptan; Furosemide
Intervention MeSH terms: Furosemide; Tolvaptan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Hyponatremia is a common finding in acute heart failure (HF) patients and is associated with
      worse prognosis. In addition to its prognostic value, hyponatremia may have importance during
      the acute management of HF. We've recently shown that acute or chronic hyponatremia,
      especially <130 mEq/L, was associated with higher loop diuretic dose requirements and more
      frequent need for escalation of the diuretic regimen to achieve the same level of diuresis as
      normonatremic HF patients. Aquaresis with tolvaptan represents a potentially advantageous
      approach to the management of volume overload in HF, especially in patients presenting with
      concomitant hyponatremia. The purpose of the current study is to prospectively evaluate the
      comparative efficacy and safety of a tolvaptan-based diuretic regimen compared to
      conventional diuresis with a furosemide-based regimen on short-term clinical and treatment
      outcomes in hyponatremic acute HF patients.

      This will be a prospective, open-label, parallel-group, randomized study comparing a
      tolvaptan-based aquaretic regimen to a conventional continuous infusion loop diuretic-based
      regimen of furosemide. Up to 55 (target sample size of 50) adult subjects admitted with acute
      HF and signs of volume overload, and serum sodium less than 135 mEq/L will be randomized to
      tolvaptan or furosemide treatment arms. The initial 24 hours of study treatment will compare
      tolvaptan monotherapy to furosemide monotherapy. After the initial 24 hours, treatment
      regimens may be altered to achieve desired clinical goals. Patients will be followed for up
      to 96 hours and at discharge for study purposes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute HF with signs or symptoms of volume overload [i.e. elevated jugular venous
             pulsation (JVP), rales, edema]

          -  Serum sodium < 135 mEq/L at time of or within first 48 hours of hospitalization

          -  Randomized within 48 hours of presentation to hospital

          -  ≥ 18 years of age

          -  Informed consent

        Exclusion Criteria:

          -  Severe symptomatic hyponatremia requiring acute treatment

          -  Severe renal impairment upon admission (creatinine clearance < 20 mL/min)

          -  Renal replacement therapy dependent, or requiring upon admission

          -  Acute coronary syndrome on admission

          -  Requires or has a mechanical circulatory support device

          -  Evidence of cardiogenic shock requiring intravenous vasopressors

          -  Pregnancy

          -  Patient requiring concomitant use of strong CYP3A4 inhibitors (clarithromycin,
             ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone,
             and telithromycin)