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HyponatremiaPhase 3SALACIANCT01227512

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

A Phase 3 study testing tolvaptan and Fluid Restriction in people with Hyponatremia and Dilutional Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 56 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tolvaptan and Fluid Restriction
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
56 sitesUnited States
Study dates
Oct 2010to May 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 21Show fewer
  • 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

Trial locations and contacts

56 sites in 1 country.

56 sites in 1 country

United States56 sites
  • Otsuka Investigational Site

    Azusa, California, 91702

  • Otsuka Investigational Site

    Baltimore, Maryland, 21215

  • Otsuka Investigational Site

    Banning, California, 92220

  • Otsuka Investigational Site

    Bethleham, Pennsylvania, 18017

  • Otsuka Investigational Site

    Birmingham, Alabama, 35216

  • Otsuka Investigational Site

    Birmingham, Alabama, 35242

  • Otsuka Investigational Site

    Buffalo, New York, 14203

  • Otsuka Investigational Site

    Buffalo, New York, 14215

  • Otsuka Investigational Site

    Cincinnati, Ohio, 45267

  • Otsuka Investigational Site

    Cleveland, Ohio, 44195

  • Otsuka Investigational Site

    Columbus, Ohio, 43212

  • Otsuka Investigational Site

    Culver City, California, 90232

  • Otsuka Investigational Site

    Denver, Colorado, 80210

  • Otsuka Investigational Site

    Elizabethtown, Kentucky, 42701

  • Otsuka Investigational Site

    Fairfax, Virginia, 22030

  • Otsuka Investigational Site

    Fairfield, Ohio, 45014

  • Otsuka Investigational Site

    Fountain Valley, California, 92708

  • Otsuka Investigational Site

    Galveston, Texas, 77555

  • Otsuka Investigational Site

    Grand Island, Nebraska, 68803

  • Otsuka Investigational Site

    Haddon Heights, New Jersey, 08035

  • Otsuka Investigational Site

    Houston, Texas, 77030

  • Otsuka Investigational Site

    Jackson, Mississippi, 39216

  • Otsuka Investigational Site

    Jacksonville, Florida, 32207

  • Otsuka Investigational Site

    Jacksonville, Florida, 32209

  • Otsuka Investigational Site

    Jacksonville, Florida, 32216

  • Otsuka Investigational Site

    Jamaica, New York, 11418

  • Otsuka Investigational Site

    Los Angeles, California, 90025

  • Otsuka Investigational Site

    Los Angeles, California, 90033

  • Otsuka Investigational Site

    Madison, Wisconsin, 53705

  • Otsuka Investigational Site

    Minneapolis, Minnesota, 55455

  • Otsuka Investigational Site

    Mission, Texas, 78572

  • Otsuka Investigational Site

    Mobile, Alabama, 36608

  • Otsuka Investigational Site

    New York, New York, 10032

  • Otsuka Investigational Site

    Newark, New Jersey, 07103

  • Otsuka Investigational Site

    Northridge, California, 91324

  • Otsuka Investigational Site

    Oklahoma City, Oklahoma, 73120

  • Otsuka Investigational Site

    Omaha, Nebraska, 68131

  • Otuska Investigational Site

    Orange, California, 92868

  • Otsuka Investigational Site

    Orlando, Florida, 32803

  • Otsuka Investigational Site

    Philadelphia, Pennsylvania, 19102

  • Otsuka Investigational Site

    Philadelphia, Pennsylvania, 19140

  • Otsuka Investigational Site

    Port Charlotte, Florida, 33952

  • Otsuka Investigational Site

    Providence, Rhode Island, 02903

  • Otsuka Investigational Site

    Rochester, Minnesota, 55905

  • Otsuka Investigational Site

    Saginaw, Michigan, 48602

  • Otsuka Investigational Site

    San Antonio, Texas, 78205

  • Otsuka Investigational Site

    San Antonio, Texas, 78229

  • Otsuka Investigational Site

    Savannah, Georgia, 31405

  • Otsuka Investigational Site

    Southfield, Michigan, 48075

  • Otsuka Investigational Site

    Springfield, Massachusetts, 01107

  • Otsuka Investigational Site

    St Louis, Missouri, 63110

  • Otsuka Investigational Site

    The Bronx, New York, 10461

  • Otsuka Investigational Site

    Toledo, Ohio, 43560

  • Otsuka Investigational Site

    Washington D.C., District of Columbia, 20010

  • Otsuka Investigational Site

    West Reading, Pennsylvania, 19611

  • Otsuka Investigational Site

    Yorba Linda, California, 92886

Other trials in United States

About this study

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

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.

Being tested
tolvaptan, Fluid Restriction
Keywords
Hyponatremia, Dilutional Hyponatremia, Euvolemic Hyponatremia, Hypervolemic Hyponatremia, Fluid Restriction, Tolvaptan
Medical subject headings
Hyponatremia, Inappropriate ADH Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tolvaptanDrug

    Also called SAMSCA, OPC-41061, OPC-156

    15 mg titrated to 30 mg then 60 mg once daily as oral tablet for up to 7 days based on response.

  • Fluid RestrictionOther

    Placebo tablet once daily with prescribed daily fluid intake of 1500 mL, then intensifying to 2 lower volumes of fluid intake for up to 7 days based on response.

    Since all particpants were blinded to treatment, titration to stricter fluid restriction followed the same algorithm as tolvaptan, increasing both the level of fluid restriction and increasing the placebo "dose"

Study groups in NCT01227512
Study groupRoleWhat they receive
Tolvaptan 15-60mgExperimentalOral tablet without fluid restriction. After the initial dose, daily dose may be titrated based on response.
Receives: Drug: tolvaptan
Fluid RestrictionActive comparatorPlacebo tablet with prescribed fluid restriction. After the initial dose, level of fluid restriction may titrated based response.
Receives: Other: Fluid Restriction

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Length of Hospital Stay (LoS)

    LoS was time to clinically ready to be hospital discharged (CRBD) from study treatment initiation, disregarding prolonged hospitalization due solely to social factors.

    Measured: 45 days

Secondary outcomes (7)
  1. Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms.

    Change from baseline in blinded rater assessed CGI-S at 48 hours post-first dose or at discharge/rescue therapy, if earlier was assessed.

    The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.

    Measured: Baseline to 48 hours post dose

  2. Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms.

    Change in CGI-S of hyponatremia symptoms from pretreatment baseline at 24 and 72 hours post-first dose, or at discharge/rescue therapy if earlier was assessed.

    The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.

    Measured: Baseline to 24 and 72 hours post dose

  3. Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms.

    Change in CGI-I score at 48 hours post-first dose or discharge/rescue therapy, if earlier was assessed.

    The CGI-I is a one-question rating scale where the participant is asked to rate total improvement whether or not, in their judgment, it is due entirely to trial treatment. Compared to his/her condition at admission to the trial, how much has he/she changed? 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse

    Measured: Baseline to 48 hours post dose

  4. Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]).

    Average 24 hour AUC of serum sodium concentration change from baseline, from Day 1 Hour 0 up to 72 hours post-first dose was assessed.

    A serum sodium sample was drawn at pre-treament and 8, 24, 48, and 72 hours post-first dose. Serum sodium was also assessed between 36 and 72 hours after the last dose.

    Analysis of AUC was for daily average AUC, hence the units or AUC are mEq/L/24 hours.

    Measured: 0 to 72 hours

  5. Time to First 2-point Improvement in CGI-S Score.

    CGI-S data up to 72 hours were used to identify 2-point improvements. Please refer to outcome measure 2 for details on the scale. For the analysis of time to first 2-point improvement in CGI-S, CGI-S data up to Hour 72 were used to identify 2-point improvements. Data for participants who received rescue therapy were censored at the time of receiving rescue therapy. For participants who were discharged before Hour 72 without reaching 2-point improvement in CGI-S, data were censored at the time of discharge. Other participants who did not reach the 2-point improvement during the 72 hours also had their data censored at their last CGI-S observations within 72 hours.

    Measured: Up to 72 hours

  6. Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2.

    Percentage of responders (defined as CGI-I score of 1 = very much improved or 2 = much improved) at 48 hours post-first dose, or at discharge/rescue therapy, if earlier. Participants given rescue therapy were given a score of 7.

    Measured: 48 hours post dose

  7. Percentage of Participants Requiring Rescue Therapy for Hyponatremia

    Percentage of participants requiring rescue therapy within first 7 days of treatment for hyponatremia.

    Measured: 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionMay 2013
  4. Study completionMay 2013

Why it stopped: Recruitment challenges and results of interim futility analysis, which showed less than likely to achieve primary endpoint goal-length of hospital stay.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01227512
Sponsor's protocol ID
156-08-275
Acronym
SALACIA
Status last verified
Oct 2014
First submitted
22 Oct 2010
Last updated
30 Oct 2014
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing tolvaptan and Fluid Restriction in people with Hyponatremia and Dilutional Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 56 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Length of Hospital Stay (LoS) (time frame: 45 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2014.

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