"SALT Trial" Study of Ascending Levels of Tolvaptan in Hyponatremia

July 9, 2026 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

Multicenter, Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of the Effects of Titrated Oral Tolvaptan Tablets in Patients With Hyponatremia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 milliequivalents/liter (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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
205

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Health Care Ctr
      • Los Angeles, California, United States, 93552
        • UCLA
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
    • Colorado
      • Denver, Colorado, United States, 80262
        • University of Colorado Health Science Center
      • Denver, Colorado, United States, 80218
        • Aurora Denver Cardiology Association
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida Gainesville
      • Port Charlotte, Florida, United States, 33952
        • Charlotte Heart Group Research Ctr
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Medical College of Georgia
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospital
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417
        • Minneapolis VA Medical Center
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University Ctr for Clinical Studies
    • Montana
      • Butte, Montana, United States, 59701
        • Mercury Street Medical
    • New York
      • Great Neck, New York, United States
        • Northshore University Hospital
      • New York, New York, United States, 10010
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina, Div. of Cardiology
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center
    • Pennsylvania
      • Norristown, Pennsylvania, United States, 19401
        • The Arthur P. Noyes Research Foundation
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Baptist Clinical Research Ctr
      • Tullahoma, Tennessee, United States, 37388
        • Tennessee Center for Clinical Trials

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Hyponatremia in euvolemic or hypervolemic states, defined as serum sodium <135 mEq/L prior to randomization
  • Able to give Informed Consent.

Exclusion Criteria

  • Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods
  • Hyponatremia in hypovolemic states
  • Acute and transient hyponatremia associated with head trauma or post-operative state
  • Hyponatremia due to uncontrolled hypothyroidism or uncontrolled adrenal insufficiency
  • Cardiac surgery within 30 days of potential study enrollment, excluding percutaneous coronary interventions
  • History of a myocardial infarction within 30 days of potential study enrollment
  • History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator
  • Severe angina including angina at rest or at slight exertion and/or unstable angina
  • History of a cerebrovascular accident within the last 30 days
  • Subjects with psychogenic polydipsia may not be included, however subjects with other psychiatric illness may be included
  • Systolic arterial blood pressure < 90 mmHg
  • History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril)
  • History of drug or medication abuse within the past year,or current alcohol abuse
  • Uncontrolled diabetes mellitus defined as fasting glucose > 300 mg/dL
  • Urinary tract obstruction except benign prostatic hyperplasia (BPH) if non-obstructive
  • Previous participation in another clinical drug trial within the past 30 days
  • Previous participation in this or any other tolvaptan clinical trial
  • Terminally ill or moribund condition with little chance of short term survival
  • Serum creatinine > 3.5 mg/dL
  • Serum sodium < 120 mEq/L with associated neurologic impairment, i.e. symptoms such as apathy, confusion, seizures
  • Patients with progressive or episodic neurologic disease such as multiple sclerosis or history of multiple strokes
  • Child-Pugh score greater than 10 (unless approved)
  • Patients receiving intravenous fluids at a rate greater than KVO (Keep Vein Open)
  • Hyponatremia due to lab artifacts
  • Patients receiving arginine vasopressin (AVP) or its analogs for treatment of any condition
  • Patients receiving within 7 days of randomization, other medications for treatment of hyponatremia specifically: demeclocycline, lithium carbonate or urea
  • Patients likely requiring intravenous (IV) saline for correction of symptomatic or asymptomatic severe hyponatremia during the course of the study
  • Severe pulmonary artery hypertension
  • Hyponatremia should not be the result of any medication that can safely be withdrawn.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tolvaptan
Tolvaptan 15 mg tablet taken orally once daily for up to 30 days. Dose titration to 30 mg and then 60 mg occurred if the participant's sodium level change from the previous day was <5 mEq/L and ≤ 135 mEq/L. The dose could be decreased at the investigator's discretion.
Drug: tolvaptan
Tolvaptan tablet taken orally once daily.
Placebo Comparator: Placebo
Placebo matching tolvaptan tablet taken orally once daily for up to 30 days.
Drug: placebo matching tolvaptan
Placebo matching tolvaptan tablet taken orally once daily.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Otsuka Pharmaceutical Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Nestor Molfino, MD, Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2003

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2005

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2005

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 7, 2003

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2003

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2003

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 156-02-235

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

IPD Sharing Time Frame

Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.

IPD Sharing Access Criteria

Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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