Aquaresis Utility for Hyponatremic Acute Heart Failure Study

Condition(s) targeted: Heart Failure

Intervention: Tolvaptan (Drug); Furosemide (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: University of Southern California

Official(s) and/or principal investigator(s):
Tien Ng, PharmD, Principal Investigator, Affiliation: University of Southern California
Uri Elkayam, MD, Principal Investigator, Affiliation: University of Southern California

Overall contact:
Tien Ng, PharmD, Phone: 323-442-1840, Email: tienng@usc.edu

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 or equal to 130 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.

Official title: Aquaresis Utility for Hyponatremic Acute Heart Failure Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mean urine output at 24 hours post randomization

Secondary outcome: Mean change in serum creatinine at 24 hours post randomization

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Acute HF with signs or symptoms of volume overload [i. e. elevated jugular venous

pulsation (JVP), rales, edema]

- Serum sodium ≤ 130 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

- Evidence of cardiogenic shock or requiring intravenous vasopressors

- Pregnancy

- Patient requiring concomitant use of strong CYP3A4 inhibitors (clarithromycin,

ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, and telithromycin)

Tien Ng, PharmD, Phone: 323-442-1840, Email: tienng@usc.edu

Keck Medical Center of USC, Los Angeles, California 90033, United States; Not yet recruiting

LAC+USC Medical Center, Los Angeles, California 90033, United States; Not yet recruiting

Starting date: July 2014
Last updated: July 2, 2014