Please select the eligibility criteria that correspond to the clinical trial below.
Title: Use of Conivaptan (Vaprisol) for Hyponatremic Neuro-ICU Patients
Brief Summary: Conivaptan (Vaprisol) is FDA-Approved for the treatment of low serum sodium (hyponatremia), but there are few data in patients with neurologic disease. Very low serum sodium in patients with brain injury can be life-threatening and is associated with cerebral edema (swelling of brain tissue). This can be important in patients with brain hemorrhage, brain tumors, or stroke (cerebral infarction).

This is a pilot study to test the hypothesis that conivaptan (Vaprisol) leads to a greater increase in sodium than usual care. Patients will be randomly assigned to usual care or the lower FDA-approved dose of conivaptan (Vaprisol). We will track the use of other interventions, such as the use of hypertonic saline (concentrated salt solution), diuretics and salt tablets. A blinded co-investigator will record neurologic examination results (NIH Stroke Scale and Glasgow Coma Scale).


Options:
A: Inclusion Criteria:

* Ability to understand the purpose and risks of the study and to provide signed and dated informed consent.
* Men and women aged 18 years or older.
* History of chronic CHF defined as requiring standard HF treatment (including diuretics) for a minimum of 30 days.
* Documented LVEF by any method within 12 months prior to screening.
* The patient has clinical evidence of volume overload at the time of inclusion with at least one of the following:

  * Dyspnea
  * Pulmonary congestion (rales)
  * Peripheral edema
  * Increased jugular venous pressure and/or hepatic congestion with ascites
  * Chest x-ray consistent with CHF
  * Plasma brain natriuretic peptide (BNP) ≥150 pg/mL or N-terminal prohormone brain natriuretic peptide (NT pro-BNP) ≥450 pg/mL

Exclusion Criteria:

* Women who are pregnant (positive pregnancy test), breastfeeding, or who will not adhere to the reproductive precautions as outlined in this protocol and in the informed consent form (ICF).
* Sustained (three blood pressure measurements over 1 hour) systolic blood pressure \<90 mmHg at Screening or Day 0.
* ST segment elevation myocardial infarction or stroke within 30 days prior to Screening.
* Hemodynamically destabilizing cardiac arrhythmia within 30 days prior to Day 0.
* Clinically significant valvular disease.
* Known clinically significant obstructive, restrictive, or hypertrophic cardiomyopathy.
* Cardiac surgery or percutaneous coronary intervention within 30 days prior to Day 0.
* Major surgical procedure within 7 days prior to Day 0.
* Likely to undergo cardiac transplantation, left ventricular assist device (LVAD) or other device implantation, or other cardiac surgery within 3 months after Screening.
* Placement of implantable cardioverter defibrillator or cardiac resynchronization therapy device within 60 days prior to Day 0.
* CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid cardiomyopathy.
* Presence of any clinically significant (as determined by the Investigator) endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, oncologic, and/or other major disease that might interfere with safe and compliant participation in this study.
* Screening laboratory findings as follows:

  * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times the upper limit of normal
  * Total bilirubin \>2.0 mg/dL
  * Serum creatinine \>3.0 mg/dL
  * Hemoglobin \<9.0 g/dL
* Uncontrolled diabetes mellitus as defined by the Investigator (e.g., glycosylated hemoglobin \[HbA1c\] \>9%).
* History of chronic drug/medication abuse within the past 6 months; or current alcohol abuse.
* Co-morbid condition with an expected survival of less than 3 months.
* Known allergy to any vasopressin antagonist or any condition for which treatment with a vasopressin antagonist may present undue risk to the patient.
* Current or recent administration (within 7 days of Day 0) of prohibited medications as listed in Section 8.6.4 .
* Participation in any other investigational study of drugs or devices within 30 days prior to Screening.
B: Inclusion Criteria:

1. Subjects hospitalized for worsening heart failure and randomized within 36 hours of initial presentation.
2. Males and females 18 years of age or older.
3. NYHA Class III or IV on admission to the hospital.
4. Able to understand content of and willing to provide written informed consent
5. Dyspnea, measured by the 5-point current dyspnea scale (moderately short of breath or worse), within 2 hours of randomization and dosing.

   The following must be met within 12 hours of randomization.
6. The subject must have signs of extracellular volume expansion, defined as two or more of the following five: Signs of RHF ( jugular venous distention, pitting edema (≥1+), ascites) and/or Signs of LHF (pulmonary congestion on chest x-ray, pulmonary rales)
7. Have at least one of the following:

   * eGFR \< 60ml/min/1.73m2, OR
   * serum sodium ≤ 134 mEq/L, OR
   * urine output ≤ 125 ml/hr over anytime frame of at least 2 hours, following administration of IV furosemide of at least 40mg. See table below.

Time Period (hr) Cumulative UO (mL) 2 \<250 3 \<375 4 \<500 5 \<625 6 \<750 7 \<875 8 \<1000

Exclusion Criteria:

1. Positive urine pregnancy test for women of child bearing potential.
2. Inability to provide written informed consent.
3. Cardiac surgery within 60 days prior to study randomization.
4. Acute Coronary Syndrome (ACS) or percutaneous coronary intervention within 30 days prior to study randomization.
5. Planned revascularization procedures, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study randomization.
6. Planned electrophysiologic (EP) device implantation within 7 days following study randomization.
7. Subjects who are on cardiac mechanical support.
8. Co-morbid condition with an expected survival less than six months.
9. History of a cerebrovascular accident within the last 30 days.
10. Hemodynamically significant uncorrected primary cardiac valvular disease.
11. Hypertrophic cardiomyopathy (obstructive or non-obstructive).
12. Uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
13. History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
14. Chronic uncontrolled diabetes mellitus as determined by the investigator.
15. Supine systolic arterial blood pressure \< 90 mmHg.
16. Serum creatinine \> 3.5 mg/dL or undergoing dialysis.
17. Hemoglobin \< 9 g/dL
18. History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazepril).
19. Inability to take oral medications.
20. Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted.
21. Previous exposure to tolvaptan within 7 days prior to randomization.
22. Subjects with refractory, end-stage, heart failure defined as subjects who are appropriate candidates for specialized treatment strategies, such as ventricular assist devices, continuous positive IV inotropic therapy, or hospice care.
23. Ultrafiltration within 7 days prior to randomization or planned.
24. Active gout
25. Serum sodium \>144 mEq/L
C: Inclusion Criteria:

* Cirrhosis of the liver confirmed by ultrasound, endoscopic examination, or biochemical evidence
* Moderate or tense ascites
* Patients with hyponatremia, defined as a serum sodium concentration of ≤130 mmol/L

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
D: 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

Answer: D