"SALT Trial" Study of Ascending Levels of Tolvaptan in Hyponatremia
- Conditions
- HyponatremiasWater IntoxicationInappropriate ADH SyndromeWater-Electrolyte Imbalances
- Registration Number
- NCT00072683
- Brief Summary
This study's purpose is to determine whether tolvaptan can safely and effectively return the body's balance of sodium and water toward normal, and to characterize and quantify the potential clinical benefits of this treatment.
- Detailed Description
Hyponatremia is defined as a serum sodium concentration below the lower limit of normal and is the most frequently encountered electrolyte abnormality in hospitalized patients. Generally speaking, most cases of hyponatremia are mild. However, as the serum sodium falls below 130 mEq/L, the possibility of significant morbidity and mortality increases, and most clinicians will initiate corrective therapy for serum sodium values approaching 130 mEq/L and lower. The reasons for treating hyponatremia relate both to the symptoms, which may be quite disturbing to patients, as well as to potential outcomes including permanent neurological damage and death. There is also growing awareness of the association between hyponatremia and increased mortality in patients with heart failure.A common theme underlying the occurrence of hyponatremia whether in the setting of congestive heart failure, hepatic failure with ascites, or the syndrome of inappropriate anti-diuretic hormone (SIADH) is the non-osmotic secretion of arginine vasopressin (AVP). The presence of excess AVP leads to fluid retention and hyponatremia. Agents that antagonize AVP, causing proportionally more water diuresis than solute excretion, could offer a significant treatment option for patients with hyponatremia, compared to fluid restriction alone. Treatment of hyponatremia, particularly in clinical settings such as decompensated congestive heart failure, is difficult as conventional diuretics cause neurohormonal activation and further stimulate the inappropriate release of vasopressin, leading to additional retention of free water and aggravation of hypoosmolality. Similarly, for cirrhosis with ascites and SIADH, conventional diuretics are either minimally effective or completely contraindicated. An alternative approach to symptom relief and treatment of hyponatremia may be the use of vasopressin antagonists, which increase free water clearance with proportionally less effect on sodium excretion. Tolvaptan is an oral vasopressin antagonist with relative affinity for the V2 receptor which has been shown to induce a diuresis with proportionally more free-water than sodium loss. The current study is being undertaken in order to evaluate whether tolvaptan, an oral AVP inhibitor, will be effective in correcting mild to moderate hyponatremia, and to elucidate the effect of this correction on the subject's well-being.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 240
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method The average daily area under the curve of change from baseline in serum sodium level up to Day 4 within the double-blind on therapy period. and/or The average daily area under the curve of change from baseline in serum sodium level up to Day 30 within
- Secondary Outcome Measures
Name Time Method The average daily area under the curve of change from baseline in serum sodium level up to Day 4 within the double-blind on therapy period for patients with severe hyponatremia (serum sodium <130 mEq/L at baseline). The average daily area under the curve of change from baseline in serum sodium level up to Day 30 within the double-blind on therapy period for patients with severe hyponatremia (serum sodium <130 mEq/L at baseline). Percentage of patients with normalized serum sodium at Day 4. Percentage of patients with normalized serum sodium at Day 30. Time to first normalization in serum sodium. Change from baseline in serum sodium at Day 4. Change from baseline in serum sodium at Day 30. Percentage of patients requiring fluid restriction at any time during the double-blind on therapy period of the study. Urine output at Day 1. Change from baseline in body weight at Day 1 (hypervolemic patients only). Fluid balance at Day 1 (hypervolemic patients only). Change from baseline in the SF-12 (health survey)Physical Component Summary (PCS)and Mental Component Summary (MCS)scales at Week 1 and Day 30. Categorical change in serum sodium at Day 4 and Day 30 for patients with baseline serum sodium <130 mEq/L. Categorical change in serum sodium at Day 4 and Day 30 for patients with baseline serum sodium ≥130 mEq/L. The percentage of patients who are designated as treatment failure due to the need for saline infusion,with or without fluid restriction. Safety:Adverse events,vital signs,clinical laboratory tests,12- lead electrocardiograms. PK:Plasma tolvaptan and DM-4103 concentrations.
Trial Locations
- Locations (22)
VA Greater Los Angeles Health Care Ctr
🇺🇸Los Angeles, California, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Mercury Street Medical
🇺🇸Butte, Montana, United States
University Hospitals of Cleveland
🇺🇸Cleveland, Ohio, United States
Washington University Ctr for Clinical Studies
🇺🇸St. Louis, Missouri, United States
Minneapolis VA Medical Center
🇺🇸Minneapolis, Minnesota, United States
Charlotte Heart Group Research Ctr
🇺🇸Port Charlotte, Florida, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
The Arthur P. Noyes Research Foundation
🇺🇸Norristown, Pennsylvania, United States
Baptist Clinical Research Ctr
🇺🇸Memphis, Tennessee, United States
UCLA
🇺🇸Los Angeles, California, United States
University of Florida Gainesville
🇺🇸Gainesville, Florida, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Medical College of Georgia
🇺🇸Augusta, Georgia, United States
Northshore University Hospital
🇺🇸Great Neck, New York, United States
Tennessee Center for Clinical Trials
🇺🇸Tullahoma, Tennessee, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa Hospital
🇺🇸Iowa City, Iowa, United States
Aurora Denver Cardiology Association
🇺🇸Denver, Colorado, United States
University of North Carolina, Div. of Cardiology
🇺🇸Chapel Hill, North Carolina, United States
University of Colorado Heath Science Center
🇺🇸Denver, Colorado, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States