Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia (SALACIA)

Otsuka

Status and phase

Terminated

Phase 3

Conditions

Inappropriate ADH Syndrome

Hyponatremia

Dilutional Hyponatremia

Treatments

Drug: tolvaptan

Other: Fluid Restriction

Study type

Interventional

Funder types

Industry

Identifiers

NCT01227512

156-08-275

Details and patient eligibility

About

The purpose of this study is to determine if hospitalized patients with symptomatic hyponatremia treated with tolvaptan are in the hospital for less time than patients treated with fluid restriction. The study will also test if tolvaptan is better than fluid restriction in treating the symptoms of hyponatremia in hospitalized patients.

Enrollment

124 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Hyponatremia in clinically euvolemic or hypervolemic states, defined as serum sodium < 130 mEq/L prior to randomization
Clinically significant symptoms of hyponatremia, defined as a CGI-S score between 3-6, inclusive
Female subjects of child bearing potential who agree to remain abstinent or to practice double-barrier forms of birth control from screening through 30 days following first dose on IMP

Exclusion criteria

Women who are pregnant or breast feeding, and females of childbearing potential who are not using acceptable contraceptive methods (such as barrier contraceptives or methods that result in a failure rate of less than 1%)
Hyponatremia in hypovolemic states, defined as the presence of clinical and historical evidence of extracellular fluid volume depletion, including but not limited to skin turgor, orthostatic changes in blood pressure or heart rate, dry mucous membranes, or a response to IV saline challenge
Subjects who are likely to require prolonged hospitalization for reasons other than hyponatremia, eg. new femoral fracture, surgeries requiring extended recovery
Recent prior treatment for hyponatremia: hypertonic saline (including normal saline challenge) (within 8 hours of baseline) or urea, lithium, demeclocycline, conivaptan or tolvaptan (within 4 days of baseline). Includes any treatment, other than fluid restriction for the purpose of increasing serum sodium.
Hyponatremia symptoms of a severity (eg, CGI = 7) such that they require immediate intervention with hypertonic saline; or are expected to require such therapy within 48 hours
Causes of neurological symptoms which are attributable to psychological (psychosis), structural (dementia of the Alzheimer's type, stroke, transient ischemic attack, multi-infarct dementia) or other metabolic causes (eg. hyper- or hypo-: oxemia, glycemia, calcemia, ammonemia, etc)
Acute and transient hyponatremia associated with head trauma or severe neurological injury (eg. stroke, subdural hematoma)or the use of recreational drugs.
History of hyponatremia known to be due to severe, untreated hypothyroidism/adrenal insufficiency
Subjects with psychogenic polydipsia
Systolic arterial blood pressure < 90 mmHg at screening
History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril), or tolvaptan
History of drug or medication abuse within the 3 months prior to screening, or current alcohol abuse
Uncontrolled diabetes mellitus defined as glucose > 300 mg/dL [16.7 mmol/L]
Current urinary tract obstruction (eg, obstructive benign prostatic hypertrophy)
Current condition of anuria
Serum creatinine > 3.5 mg/dL at screening
Terminally ill or moribund condition with little chance of short-term (eg, 30 day) survival
Subjects whose hyponatremia is the result of any medication that can safely be withdrawn (examples of drugs often not withdrawn include: anticonvulsants [eg, carbamazepine] and antipsychotics [eg, haloperidol])
Patients receiving DDAVP within 2 days of screening
Patients with history of active variceal bleeding within the past 30 days, without prior approval from sponsor medical monitor
Participation in another investigational drug trial within the past 30 days