Aquaresis Utility for Hyponatremic Acute Heart Failure Study

Study Overview
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Brief Summary
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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.

Official Title
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Aquaresis Utility for Hyponatremic Acute Heart Failure Study

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Tolvaptan
* Drug: Furosemide


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolvaptan<br>Tolvaptan 30-60mg once daily (with rescue loop diuretic or metolazone) | Drug: Tolvaptan<br> <br> * Other names: Samsca;|
| Active Comparator: Furosemide<br>Furosemide continuous infusion 5mg/h with option to titrate (with rescue metolazone) | Drug: Furosemide<br> <br> * Other names: Lasix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Urine Output at 24 Hours Post Randomization |  | 24 hours post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Change in Serum Creatinine at 24 Hours Post Randomization | Comparison between baseline and 24 hours post randomization concentrations. | 24 hours post randomization |