Clinical trial NCT02183792: Aquaresis Utility for Hyponatremic Acute Heart Failure Study
Official title: Aquaresis Utility for Hyponatremic Acute Heart Failure Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Otsuka America Pharmaceutical
First posted: 2014-07-08
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Median Urine Output at 24 Hours Post Randomization
timeFrame: 24 hours post randomization
Secondary outcomes:
measure: Median Change in Serum Creatinine at 24 Hours Post Randomization
timeFrame: 24 hours post randomization
Other outcomes:
measure: Total Urine Output
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Glomerular Filtration Rate (Estimated)
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: In-hospital Mortality
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Mean Hourly Urine Output at 24 Hours
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Serum Sodium Change
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Weight Change
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Cumulative Furosemide Dose
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Cumulative Metolazone Use
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Change in Self-rated Dyspnea
timeFrame: At baseline, 24 and 96 hours post randomization
measure: Acute Worsening of Kidney Function (Defined as an Increase in Serum Creatinine 0.3 mg/dL or 25% Above Baseline)
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Incidence of Electrolyte Abnormalities
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Symptomatic Hypotension
timeFrame: Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
measure: Change in Plasma Renin Activity
timeFrame: At baseline, 24 and 96 hours post randomization
measure: Change in Copeptin
timeFrame: At baseline, 24 and 96 hours post randomization
measure: Change in N-terminal Pro-B-type Natriuretic Peptide
timeFrame: At baseline, 24 and 96 hours post randomization
measure: Change in Cystatin C
timeFrame: At baseline, 24 and 96 hours post randomization
measure: Change in Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL)
timeFrame: At baseline, 24, 48, 72 and 96 hours post randomization
measure: Hospital Length of Stay
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 5 days
Locations:
city: Los Angeles
country: United States
facility: Keck Medical Center of USC
state: California
city: Los Angeles
country: United States
facility: LAC+USC Medical Center
state: California
Study officials:
affiliation: University of Southern California
name: Tien Ng, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Uri Elkayam, MD
role: PRINCIPAL_INVESTIGATOR
References: