Aquaresis Utility for Hyponatremic Acute Heart Failure Study

Heart Failure Clinical Trial

— AQUA-AHF  

Official title:

Aquaresis Utility for Hyponatremic Acute Heart Failure Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02183792
• Other study ID #: HS-13-00705
• Status: Completed
• Phase: Phase 4
• Start date: December 2014
• Est. completion date: March 2018

Study information

• Verified date: May 2019
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Tolvaptan

• Furosemide

Locations

Country	Name	City	State
United States	Keck Medical Center of USC	Los Angeles	California
United States	LAC+USC Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	Otsuka America Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total Urine Output		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Glomerular Filtration Rate (Estimated)		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	In-hospital Mortality		Participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Mean Hourly Urine Output at 24 Hours		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Serum Sodium Change	Difference assessed at baseline, 8, 24, 48, 72 and 96 hours.	Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Weight Change	Difference assessed at baseline, 8, 24, 48, 72 and 96 hours.	Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Cumulative Furosemide Dose		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Cumulative Metolazone Use		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Change in Self-rated Dyspnea		At baseline, 24 and 96 hours post randomization
Other	Acute Worsening of Kidney Function (Defined as an Increase in Serum Creatinine 0.3 mg/dL or 25% Above Baseline)		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Incidence of Electrolyte Abnormalities	Hypo- and hyperkalemia defined as outside the range of 3.5 to 5.0 mEq/L Hypo- and hypermagnesemia defined as outside the range of 1.5-2.4 mEq/L	Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Symptomatic Hypotension		Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Other	Change in Plasma Renin Activity		At baseline, 24 and 96 hours post randomization
Other	Change in Copeptin		At baseline, 24 and 96 hours post randomization
Other	Change in N-terminal Pro-B-type Natriuretic Peptide		At baseline, 24 and 96 hours post randomization
Other	Change in Cystatin C		At baseline, 24 and 96 hours post randomization
Other	Change in Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL)		At baseline, 24, 48, 72 and 96 hours post randomization
Other	Hospital Length of Stay		Participants will be followed for the duration of hospital stay, an expected average of 5 days
Primary	Median Urine Output at 24 Hours Post Randomization		24 hours post randomization
Secondary	Median Change in Serum Creatinine at 24 Hours Post Randomization	Comparison between baseline and 24 hours post randomization concentrations.	24 hours post randomization