Please select the eligibility criteria that correspond to the clinical trial below.
Title: Protocol 156-03-236: Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long Term Efficacy and Safety of Oral Tolvaptan Tablets in Subjects Hospitalized With Worsening Congestive Heart Failure
Brief Summary: The purpose of this study is to compare the effectiveness of tolvaptan or placebo in adults with worsening congestive heart failure (CHF).


Options:
A: Inclusion Criteria:

* Age greater than or equal to 18 years.
* Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to randomization. Chronic heart failure is defined as requiring treatment for a minimum of 30 days prior to hospitalization.

The subject must have signs of extracellular volume expansion, defined as two or more of the following: a) jugular venous distention; b) pitting edema (\>1+); or c) dyspnea.

* NYHA Class III or IV at the time of hospitalization.
* Left Ventricular Ejection Fraction \< = 40% within one year.

Exclusion Criteria

* Women who will not adhere to the reproductive precautions as outlined in the Informed Consent form.
* Positive urine pregnancy test.
* Inability to provide written informed consent.
* Cardiac surgery within 60 days of potential study enrollment, excluding percutaneous coronary interventions.
* Planned revascularization procedures, electrophysiologic (EP) device implantation, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study enrollment.
* Subjects who are on cardiac mechanical support.
* History of bi-ventricular pacer placement within the last 60 days.
* Co-morbid condition with an expected survival less than six months.
* Subjects with acute ST segment elevation myocardial infarction at the time of hospitalization.
* History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator.
* History of a cerebrovascular accident within the last 30 days.
* Hemodynamically significant uncorrected primary cardiac valvular disease.
* Hypertrophic cardiomyopathy (obstructive or non-obstructive).
* CHF due to uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
* Subjects with progressive or episodic neurological disease such as multiple sclerosis or history of multiple strokes.
* History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
* History of poorly controlled diabetes mellitus.
* Morbid obesity, defined as \> 159 kg (or 350 lbs) or BMI \> 40.
* Supine systolic arterial blood pressure \< 90 mmHg.
* Serum creatinine \> 3.5 mg/dL or \> 309.4 mmol/L.
* Serum potassium \> 5.5 mEq/L or \> 5.5 mmol/L.
* Hemoglobin \< 9 g/dL or \< 90 g/L.
* History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazapril).
* History of drug or medication abuse within the past year, or current alcohol abuse.
* Inability to take oral medications.
* Participation in another clinical drug or device trial within the past 30 days.
* Previous participation in this or any other tolvaptan clinical trial.
B: 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.
C: Inclusion Criteria:

* Cirrhosis of the liver confirmed by ultrasound, endoscopic examination or biochemical evidence
* Patients having undergone therapeutic paracentesis for the removal of ascites in the previous 24 hours with the removal of ≥4 L of fluid
* Patients having undergone at least 1 other therapeutic paracentesis in the previous 3 months

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

* Male or Female patients aged 18 higher
* Dilutional Hyponatremia with serum sodium between 115 and 132 mmol/L
* Ability to give written informed consent (the informed consent may be signed by a legally authorized representative if the patient is unable to sign)

Exclusion Criteria:

* Presence of known or untreated adrenal insufficiency, SIADH or cirrhosis, or hyperthyroidism
* Presence of signs of hypovolemia
* Administration of other V2 receptor antagonists or demeclocycline or lithium within one month and urea within two days prior to study drug administration
* Presence of uncontrolled diabetes with fasting glycemia ³ 200 mg/dL (³ 11.09 mmol/L)
* Patients considered by the Investigator unsuitable candidates to receive an investigational drug (e.g., presence of any neurological symptoms that may worsen in five days, based on the judgment of the Investigator, or presence of any neurological symptoms for which the persistence of hyponatremia over several days may be deleterious)
* Administration of inducers of CYP3A4 (phenobarbital, phenytoin, rifampin, Saint John's Wort) or potent and moderate inhibitors of CYP3A4 within two weeks prior to study drug administration
* Presence or history of allergic reaction to SR121463B8
* Previous study with SR121463B
* Inadequate hematological, renal, and hepatic functions: hemoglobin (Hb) \< 9 g/dL, neutrophils \< 1,500/mm3, platelets \< 100,000/mm3, serum creatinine \> 175 mol/L (or clearance of creatinine \< 30 mL/min for sites where Ethics Committees require this parameter), serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 2 x upper limit of normal (ULN)
* QTCB 500 ³ ms
* Positive pregnancy test and absence of medically approved contraceptive methods (e.g., surgical sterilization of more than one month duration, oral contraception or intrauterine device in combination with either diaphragm, condom, or spermicide) for females of childbearing potential
* Pregnancy or breast-feeding

Answer: A