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Tolvaptan for In-hospital Hyponatremia (INSERT)

Primary Purpose

Hyponatremia

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Tolvaptan
Standard therapy
Sponsored by
Mario Negri Institute for Pharmacological Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyponatremia focused on measuring Hyponatremia, Vasopressin, Tolvaptan, SIADH

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

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 prior to the potential study enrollment, excluding percutaneous coronary interventions;
  • History of a myocardial infarction within 30 days prior to the potential study enrollment;
  • 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.

Sites / Locations

  • OO.RR., Bergamo - Unit of Nephrology and Dialisis

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Tolvaptan

standard therapy

Arm Description

Outcomes

Primary Outcome Measures

Changes from baseline in proportion of subjects with normonatremia at 6 month.
Changes from baseline in serum sodium levels from basal at 6 months.

Secondary Outcome Measures

Proportion of subjects achieving normonatremia at discharge and at predefined time-points.
Absolute changes in serum sodium levels vs baseline at predefined time-points.

Full Information

First Posted
June 24, 2011
Last Updated
December 14, 2016
Sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
A.O. Ospedale Papa Giovanni XXIII
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1. Study Identification

Unique Protocol Identification Number
NCT01386372
Brief Title
Tolvaptan for In-hospital Hyponatremia
Acronym
INSERT
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Terminated
Why Stopped
futility
Study Start Date
June 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mario Negri Institute for Pharmacological Research
Collaborators
A.O. Ospedale Papa Giovanni XXIII

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyponatremia
Keywords
Hyponatremia, Vasopressin, Tolvaptan, SIADH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tolvaptan
Arm Type
Experimental
Arm Title
standard therapy
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Tolvaptan
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Standard therapy
Intervention Description
Fluid restriction, normal or hypertonic saline, furosemide.
Primary Outcome Measure Information:
Title
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..
Title
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..
Secondary Outcome Measure Information:
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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 prior to the potential study enrollment, excluding percutaneous coronary interventions; History of a myocardial infarction within 30 days prior to the potential study enrollment; 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.
Facility Information:
Facility Name
OO.RR., Bergamo - Unit of Nephrology and Dialisis
City
Bergamo
ZIP/Postal Code
24128
Country
Italy

12. IPD Sharing Statement

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Tolvaptan for In-hospital Hyponatremia

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