Aquaresis Utility for Hyponatremic Acute Heart Failure Study (AQUA-AHF)
Primary Purpose
Heart Failure
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Tolvaptan
Furosemide
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure
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)
Sites / Locations
- Keck Medical Center of USC
- LAC+USC Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tolvaptan
Furosemide
Arm Description
Tolvaptan 30-60mg once daily (with rescue loop diuretic or metolazone)
Furosemide continuous infusion 5mg/h with option to titrate (with rescue metolazone)
Outcomes
Primary Outcome Measures
Median Urine Output at 24 Hours Post Randomization
Secondary Outcome Measures
Median Change in Serum Creatinine at 24 Hours Post Randomization
Comparison between baseline and 24 hours post randomization concentrations.
Full Information
NCT ID
NCT02183792
First Posted
June 25, 2014
Last Updated
May 24, 2019
Sponsor
University of Southern California
Collaborators
Otsuka America Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT02183792
Brief Title
Aquaresis Utility for Hyponatremic Acute Heart Failure Study
Acronym
AQUA-AHF
Official Title
Aquaresis Utility for Hyponatremic Acute Heart Failure Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
February 2018 (Actual)
Study Completion Date
March 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Southern California
Collaborators
Otsuka America Pharmaceutical
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tolvaptan
Arm Type
Experimental
Arm Description
Tolvaptan 30-60mg once daily (with rescue loop diuretic or metolazone)
Arm Title
Furosemide
Arm Type
Active Comparator
Arm Description
Furosemide continuous infusion 5mg/h with option to titrate (with rescue metolazone)
Intervention Type
Drug
Intervention Name(s)
Tolvaptan
Other Intervention Name(s)
Samsca
Intervention Type
Drug
Intervention Name(s)
Furosemide
Other Intervention Name(s)
Lasix
Primary Outcome Measure Information:
Title
Median Urine Output at 24 Hours Post Randomization
Time Frame
24 hours post randomization
Secondary Outcome Measure Information:
Title
Median Change in Serum Creatinine at 24 Hours Post Randomization
Description
Comparison between baseline and 24 hours post randomization concentrations.
Time Frame
24 hours post randomization
Other Pre-specified Outcome Measures:
Title
Total Urine Output
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Glomerular Filtration Rate (Estimated)
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
In-hospital Mortality
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Mean Hourly Urine Output at 24 Hours
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Serum Sodium Change
Description
Difference assessed at baseline, 8, 24, 48, 72 and 96 hours.
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Weight Change
Description
Difference assessed at baseline, 8, 24, 48, 72 and 96 hours.
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Cumulative Furosemide Dose
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Cumulative Metolazone Use
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Change in Self-rated Dyspnea
Time Frame
At baseline, 24 and 96 hours post randomization
Title
Acute Worsening of Kidney Function (Defined as an Increase in Serum Creatinine 0.3 mg/dL or 25% Above Baseline)
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Incidence of Electrolyte Abnormalities
Description
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
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Symptomatic Hypotension
Time Frame
Up to 96 hours post randomization and participants will be followed for the duration of hospital stay, an expected average of 5 days
Title
Change in Plasma Renin Activity
Time Frame
At baseline, 24 and 96 hours post randomization
Title
Change in Copeptin
Time Frame
At baseline, 24 and 96 hours post randomization
Title
Change in N-terminal Pro-B-type Natriuretic Peptide
Time Frame
At baseline, 24 and 96 hours post randomization
Title
Change in Cystatin C
Time Frame
At baseline, 24 and 96 hours post randomization
Title
Change in Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL)
Time Frame
At baseline, 24, 48, 72 and 96 hours post randomization
Title
Hospital Length of Stay
Time Frame
Participants will be followed for the duration of hospital stay, an expected average of 5 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tien Ng, PharmD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Uri Elkayam, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
Keck Medical Center of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
LAC+USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
12. IPD Sharing Statement
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Aquaresis Utility for Hyponatremic Acute Heart Failure Study
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