Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of the Effects of Titrated Oral Tolvaptan Tablets in Patients With Hyponatremia
Data Collection
Brain Diseases+10
+ Central Nervous System Diseases
+ Endocrine System Diseases
Treatment Study
Summary
Study start date: April 1, 2003
Actual date on which the first participant was enrolled.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 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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.240 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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. 10) 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. * 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 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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 22 locations
UCLA
Los Angeles, United StatesUCSF Medical Center
San Francisco, United StatesAurora Denver Cardiology Association
Denver, United States