Please select the eligibility criteria that correspond to the clinical trial below.
Title: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of the Effects of Titrated Oral Tolvaptan Tablets in Patients With Hyponatremia
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* severe hyponatremia (Na \< 130 mmol/L) or
* symptomatic hyponatremia - Na \< 135 mmol/L for at least six hours with Glasgow Coma Scale \< 15

Exclusion Criteria:

* Enrollment in the NMH high-risk spine protocol. These patients receive large amounts of fluids, have rapid changes in electrolytes, and are typically corrected in 48 hours
* Expected death from any cause
* Known sensitivity or allergy to conivaptan
* Renal failure (baseline creatinine \> 1.5 mg/dL)
* Clinical diagnosis of hypovolemia, or by central venous pressure (CVP) \< 5 mm Hg if a central venous catheter is in place
* Concomitant use of potent inhibitors of cytochrome P-450 isoenzyme 3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir). These agents are not commonly used in the Neuro-ICU
* Clinical diagnosis of liver failure or insufficiency
* Pregnancy (must be excluded before entry)
* Lack of informed consent from the patient or a legally authorized representative (LAR)
* Use of intra-arterial vasodilators (e.g. verapamil, nicardipine) within 24 hours (e.g. for vasospasm after SAH)
* Concern by the Neuro-ICU pharmacist of a drug-drug interaction that would meaningfully impact care (the Neuro-ICU pharmacist will review the medication regimen before recruitment)
* Patients with a diagnosis of diabetes insipidus or treated with vasopressin, since these patients are already treated for abnormal free water balance
* Patients with congestive heart failure, since this is an approved use of the drug (these patients are typically not cared for in the Neuro-ICU)
* Age\<18 years (these patients are not cared for at NMH)
* Inclusion declined by the attending physician or consulting study nephrologist
B: Inclusion Criteria:

* Patients with cirrhosis of the liver.
* Patients resistant to the effects of diuretics, intolerant of diuretics or otherwise unsuitable for treatment with diuretics according to the judgement of the investigator.
* Patients with recurrent ascites having undergone both of the following:

  * therapeutic paracentesis for the removal of ascites in the previous 24 hours with the removal of = or \> 4 litres of fluid.
  * at least one other therapeutic paracentesis in the previous 3 months.

Exclusion Criteria:

* Patients with an existing functional transjugular intrahepatic portosystemic shunt (TIPS) or other shunt.
* Known hepatocellular carcinoma.
* Patients with ascites of cardiac origin or due to peritoneal infection (e.g. tuberculosis) or peritoneal carcinoma
* Patients previously exposed to satavaptan in the past 12 months.
C: 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
D: Inclusion Criteria:

* In emergency setting (2016.6-) and/or inpatients at ward (2018.9-)
* Glucose corrected serum sodium ≤125 mmol/L
* Patients with moderately severe or severe symptom

  * Moderately severe

    :Nausea without vomiting Drowsy, Headache General weakness, myalgia
  * Severe :Vomiting, Stupor, Seizures, Coma (Glasgow Coma Scale ≤8)
* written consent

Exclusion Criteria:

* Pseudohyponatremia: serum osmolality \> 275 mOsm/kg

  - If the serum osmolality is \> 275 mOsm/kg but the BUN is ≥ 30 mg/dL, the patients can be registered if calculated serum osmolality (2 x plasma \[Na\] + \[Glucose\]/18) is \<275 mOsm/kg
* Primary polydipsia: urine osmolality ≤ 100 mOsm/kg
* Glucose corrected serum sodium \>125 mmol/L
* Arterial hypotension (SBP \<90mmHg and MAP \<70mmHg)
* Anuria or urinary outlet obstruction
* Liver disease

  * transaminase levels \>3 times the upper limit normal
  * Known LC with ascites or diuretics use or PSE Hx or Varix Hx
* Uncontrolled diabetes mellitus (HbA1C \> 9%)
* Women who are pregnant or breast feeding
* History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, cebrovascular trauma, and increased intracranial pressure within the 3 months prior to randomization

Answer: C