HyponatremiaPhase 2INSERTNCT01386372
Tolvaptan for In-hospital Hyponatremia
A Phase 2 study testing Tolvaptan and Standard therapy in people with Hyponatremia, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
Trial summary
Hyponatremia is a common electrolyte disorder encountered in hospitalized patients. A preliminary, observational, feasibility analysis finalized to assess retrospectively the incidence of hyponatremia (Serum sodium < 135 mEq/L) in a general medical-surgical hospital and the distribution of the cases of hyponatremia… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hyponatremia
- What is being tested?
- Tolvaptan and Standard therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2011to Nov 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non artifactual hyponatremia in euvolemic or hypervolemic states, defined as serum sodium <135 mEq/L confirmed in at least 2 consecutive evaluations;
- 18 years of age or older;
- Able to give written Informed Consent.
Who cannot join
- 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 prior to the potential study enrollment, excluding percutaneous coronary interventions;
- History of a myocardial infarction within 30 days prior to the potential study enrollment;
Show all 27Show fewer
- History of sustained ventricular tachycardia or ventricular fibrillation within the last 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 >300mg/dL;
- Urinary tract obstruction except BPH if non-obstructive;
- 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 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 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study To Evaluate The Incidence Of Hyponatremia In A Medical-Surgical Hospital And To Explore The Efficacy And Safety Of Tolvaptan In The Clinical Practice
Hyponatremia is a common electrolyte disorder encountered in hospitalized patients. A preliminary, observational, feasibility analysis finalized to assess retrospectively the incidence of hyponatremia (Serum sodium < 135 mEq/L) in a general medical-surgical hospital and the distribution of the cases of hyponatremia among different referral units showed that over one year observation there were more than 1500 cases of hyponatremia. Conventional therapy for hyponatremia depends on its causes, speed of onset, extracellular fluid volume status, and severity. Treatment consists in fluid restriction, normal or hypertonic saline, furosemide. Recent development of arginine vasopressin antagonists has provided a new therapeutic option for treatment of hyponatremia.Tolvaptan, an orally administered, nonpeptide, selective vasopressin V2 receptor antagonist reported to increase free water clearance and limit fluid retention in subjects with congestive heart failure or liver cirrhosis, has been also shown to be effective in the treatment of chronic hyponatremia in patients with SIADH, chronic heart failure, liver cirrhosis. Thus the investigators designed a clinical study to explore the incidence of severe hyponatremia in hospitalized patients in the setting of large general hospital and to evaluate whether tolvaptan is effective and safe in increasing serum sodium concentration in patients with normovolemic and hypervolemic hyponatremia in the setting of daily clinical practice. Moreover this study may help understand the cost-effectiveness of tolvaptan therapy compared to traditional treatments of hyponatremia.
- Conditions
- Hyponatremia
- Being tested
- Tolvaptan, Standard therapy
- Keywords
- Hyponatremia, Vasopressin, Tolvaptan, SIADH
- Medical subject headings
- Hyponatremia, Diabetes Insipidus, Inappropriate ADH Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Patients will receive full-dose oral tolvaptan therapy up to 1 month after randomization. During the initial 4 days of therapy, the dose of the study drug will be increased from 15 to 30 mg or from 30 to 60 mg according to a regimen designed for slow correction of serum sodium concentrations to 135 mEq/L or more Depending on the serum sodium concentration the dose will be increased or decreased. Patients will then be continued on their maintenance therapy with adjustments allowed to prevent hyponatremia and avoiding hypernatremia. As soon as normal serum sodium levels are achieved in at least two consecutive measurements the dose of the study drug will be progressively tapered according to an individually tailored weaning program
Standard therapyOther
Fluid restriction, normal or hypertonic saline, furosemide.
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Experimental | Not described Receives: Drug: Tolvaptan |
| standard therapy | Active comparator | Not described Receives: Other: Standard therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline in proportion of subjects with normonatremia at 6 month.
Measured: At 1,2,3,4 and 10 day, and at 1,2,4 and 6 month..
Changes from baseline in serum sodium levels from basal at 6 months.
Measured: At 1,2,3,4, 10 day and at 1,2,4 and 6 month..
Secondary outcomes (2)
Proportion of subjects achieving normonatremia at discharge and at predefined time-points.
Measured: 8 hours, 1, 2, 3, and 10 days and 1, 2, 4 and 6 months after randomization
Absolute changes in serum sodium levels vs baseline at predefined time-points.
Measured: 8 hours, 1, 2, 3, and 10 days and 1, 2, 4 and 6 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study startJun 2011
- Primary completionNov 2012
- Study completionNov 2012
Why it stopped: futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyponatremiaStudies of the same condition, open and under way.
- More trials run by Mario Negri Institute for Pharmacological ResearchThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- A.O. Ospedale Papa Giovanni XXIII
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386372
- Sponsor's protocol ID
- INSERT
- Other IDs
- 2010-024431-17
- Acronym
- INSERT
- Status last verified
- Feb 2013
- First submitted
- 24 Jun 2011
- Last updated
- 15 Dec 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study To Evaluate The Incidence Of Hyponatremia In A Medical-Surgical Hospital And To Explore The Efficacy And Safety Of Tolvaptan In The Clinical Practice
- ClinicalTrials.gov ID
- NCT01386372
- Acronym / sponsor ID
- INSERT / INSERT
- Conditions
- Hyponatremia
- Keywords
- Hyponatremia, Vasopressin, Tolvaptan, SIADH
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: futility
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Collaborators
- A.O. Ospedale Papa Giovanni XXIII
- Study start
- Jun 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 1 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hyponatremia is a common electrolyte disorder encountered in hospitalized patients. A preliminary, observational, feasibility analysis finalized to assess retrospectively the incidence of hyponatremia (Serum sodium < 135 mEq/L) in a general medical-surgical hospital and the distribution of the cases of hyponatremia among different referral units showed that over one year observation there were more than 1500 cases of hyponatremia. Conventional therapy for hyponatremia depends on its causes, speed of onset, extracellular fluid volume status, and severity. Treatment consists in fluid restriction, normal or hypertonic saline, furosemide. Recent development of arginine vasopressin antagonists has provided a new therapeutic option for treatment of hyponatremia.Tolvaptan, an orally administered, nonpeptide, selective vasopressin V2 receptor antagonist reported to increase free water clearance and limit fluid retention in subjects with congestive heart failure or liver cirrhosis, has been also shown to be effective in the treatment of chronic hyponatremia in patients with SIADH, chronic heart failure, liver cirrhosis. Thus the investigators designed a clinical study to explore the incidence of severe hyponatremia in hospitalized patients in the setting of large general hospital and to evaluate whether tolvaptan is effective and safe in increasing serum sodium concentration in patients with normovolemic and hypervolemic hyponatremia in the setting of daily clinical practice. Moreover this study may help understand the cost-effectiveness of tolvaptan therapy compared to traditional treatments of hyponatremia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Experimental | Drug: Tolvaptan |
| standard therapy | Active comparator | Other: Standard therapy |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Non artifactual hyponatremia in euvolemic or hypervolemic states, defined as serum sodium <135 mEq/L confirmed in at least 2 consecutive evaluations;
- 18 years of age or older;
- Able to give written Informed Consent.
Key exclusion criteria (27 listed)
- 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 prior to the potential study enrollment, excluding percutaneous coronary interventions;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolvaptanPatients will receive full-dose oral tolvaptan therapy up to 1 month after randomization. During the initial 4 days of therapy, the dose of the study drug will be increased from 15 to 30 mg or from 30 to 60 mg according to a regimen designed for slow correction of serum sodium concentrations to 135 mEq/L or more Depending on the serum sodium concentration the dose will be increased or decreased. Patients will then be continued on their maintenance therapy with adjustments allowed to prevent hyponatremia and avoiding hypernatremia. As soon as normal serum sodium levels are achieved in at least two consecutive measurements the dose of the study drug will be progressively tapered according to an individually tailored weaning program | Drug | Tolvaptan |
| Standard therapyFluid restriction, normal or hypertonic saline, furosemide. | Other | standard therapy |
Primary outcome
Changes from baseline in proportion of subjects with normonatremia at 6 month.
Time frame: At 1,2,3,4 and 10 day, and at 1,2,4 and 6 month..
Changes from baseline in serum sodium levels from basal at 6 months.
Time frame: At 1,2,3,4, 10 day and at 1,2,4 and 6 month..
2 secondary outcomes
Proportion of subjects achieving normonatremia at discharge and at predefined time-points.
Time frame: 8 hours, 1, 2, 3, and 10 days and 1, 2, 4 and 6 months after randomization
Absolute changes in serum sodium levels vs baseline at predefined time-points.
Time frame: 8 hours, 1, 2, 3, and 10 days and 1, 2, 4 and 6 months after randomization
Results and safety
The study was stopped early (reason given: futility). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tolvaptan and Standard therapy in people with Hyponatremia, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.
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 27 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 15 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: futility). Results are not available in the source record.
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?
Changes from baseline in proportion of subjects with normonatremia at 6 month. (time frame: At 1,2,3,4 and 10 day, and at 1,2,4 and 6 month..). The study lists 2 primary outcomes in all. 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 15 Dec 2016.