Clinical trial NCT01227512: Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia
Official title: Phase 3b, Multicenter, Randomized, Single-blind, Parallel Group Trial of the Effects of Titrated Oral SAMSCA(r) (Tolvaptan) 15, 30, or 60 mg QD Compared to Placebo Plus Fluid Restriction on Length of Hospital Stay and Symptoms in Subjects Hospitalized With Dilutional Hyponatremia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hyponatremia
Dilutional Hyponatremia
Inappropriate ADH Syndrome
Keywords: Hyponatremia
Dilutional Hyponatremia
Euvolemic Hyponatremia
Hypervolemic Hyponatremia
Fluid Restriction
Tolvaptan
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Length of Hospital Stay (LoS)
timeFrame: 45 days
Secondary outcomes:
measure: Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms.
timeFrame: Baseline to 48 hours post dose
measure: Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms.
timeFrame: Baseline to 24 and 72 hours post dose
measure: Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms.
timeFrame: Baseline to 48 hours post dose
measure: Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]).
timeFrame: 0 to 72 hours
measure: Time to First 2-point Improvement in CGI-S Score.
timeFrame: Up to 72 hours
measure: Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2.
timeFrame: 48 hours post dose
measure: Percentage of Participants Requiring Rescue Therapy for Hyponatremia
timeFrame: 7 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Otsuka Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Otsuka Investigational Site
state: Alabama
city: Mobile
country: United States
facility: Otsuka Investigational Site
state: Alabama
city: Azusa
country: United States
facility: Otsuka Investigational Site
state: California
city: Banning
country: United States
facility: Otsuka Investigational Site
state: California
city: Culver City
country: United States
facility: Otsuka Investigational Site
state: California
city: Fountain Valley
country: United States
facility: Otsuka Investigational Site
state: California
city: Los Angeles
country: United States
facility: Otsuka Investigational Site
state: California
city: Los Angeles
country: United States
facility: Otsuka Investigational Site
state: California
city: Northridge
country: United States
facility: Otsuka Investigational Site
state: California
city: Orange
country: United States
facility: Otuska Investigational Site
state: California
city: Yorba Linda
country: United States
facility: Otsuka Investigational Site
state: California
city: Denver
country: United States
facility: Otsuka Investigational Site
state: Colorado
city: Washington
country: United States
facility: Otsuka Investigational Site
state: District of Columbia
city: Jacksonville
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Orlando
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: Otsuka Investigational Site
state: Florida
city: Savannah
country: United States
facility: Otsuka Investigational Site
state: Georgia
city: Elizabethtown
country: United States
facility: Otsuka Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: Otsuka Investigational Site
state: Maryland
city: Springfield
country: United States
facility: Otsuka Investigational Site
state: Massachusetts
city: Saginaw
country: United States
facility: Otsuka Investigational Site
state: Michigan
city: Southfield
country: United States
facility: Otsuka Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Otsuka Investigational Site
state: Minnesota
city: Rochester
country: United States
facility: Otsuka Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: Otsuka Investigational Site
state: Mississippi
city: St. Louis
country: United States
facility: Otsuka Investigational Site
state: Missouri
city: Grand Island
country: United States
facility: Otsuka Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: Otsuka Investigational Site
state: Nebraska
city: Haddon Heights
country: United States
facility: Otsuka Investigational Site
state: New Jersey
city: Newark
country: United States
facility: Otsuka Investigational Site
state: New Jersey
city: Bronx
country: United States
facility: Otsuka Investigational Site
state: New York
city: Buffalo
country: United States
facility: Otsuka Investigational Site
state: New York
city: Buffalo
country: United States
facility: Otsuka Investigational Site
state: New York
city: Jamaica
country: United States
facility: Otsuka Investigational Site
state: New York
city: New York
country: United States
facility: Otsuka Investigational Site
state: New York
city: Cincinnati
country: United States
facility: Otsuka Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Otsuka Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Otsuka Investigational Site
state: Ohio
city: Fairfield
country: United States
facility: Otsuka Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Otsuka Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Otsuka Investigational Site
state: Oklahoma
city: Bethleham
country: United States
facility: Otsuka Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Otsuka Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Otsuka Investigational Site
state: Pennsylvania
city: West Reading
country: United States
facility: Otsuka Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: Otsuka Investigational Site
state: Rhode Island
city: Galveston
country: United States
facility: Otsuka Investigational Site
state: Texas
city: Houston
country: United States
facility: Otsuka Investigational Site
state: Texas
city: Mission
country: United States
facility: Otsuka Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Otsuka Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Otsuka Investigational Site
state: Texas
city: Fairfax
country: United States
facility: Otsuka Investigational Site
state: Virginia
city: Madison
country: United States
facility: Otsuka Investigational Site
state: Wisconsin
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Ann Dandurand, MD
role: STUDY_DIRECTOR
References: