Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 4 Study on the Comparison Between Combined Versus Sequential Diuretic Treatment of Moderate Ascites in Nonazotemic Patients With Cirrhosis
Brief Summary: The question whether the sequential diuretic therapy, that means using an antialdosteronic drug at first and adding a loop diuretic in nonresponders, is better than the combination of the two diuretics from the beginning (combined diuretic therapy) in the treatment of ascites in patients with cirrhosis is still open. Therefore, the aim of the study is to compare sequential versus combined diuretic therapy in these patients. One hundred patients will be randomized into two groups. Group A will receive potassium canrenoate at the initial dose of 200 mg/day, then increased up to 400 mg/day. Non responders will be treated with 400 mg/day of potassium canrenoate and furosemide at an initial dose of 50 mg/day, then increased up to 150 mg/day. Group B will receive at first 200 mg/day of potassium canrenoate and 50 mg/day of furosemide, then increased up to 400 mg/day and 150 mg/day, respectively.

The percentage of responders to dthe diuretic treatment, the time to get the resolution of ascites and the rate of adverse effects will be compared between the two Groups of Patients.


Options:
A: Inclusion Criteria:

* Grade 2 ascites
* Serum creatinine less than 1.2 mtg/dl
* Serum sodium \> 130 mmol/l
* Serum potassium within 3.5 and 4.5 mmol/l
* At least five days after the withdrawal of diuretics
* A 90 mmol/day Na diet.

Exclusion Criteria:

* Any therapeutic paracentesis for ascites before inclusion
* Cardiac or respiratory disease
* Gastrointestinal bleeding, hepatic encephalopathy, bacterial infections in the last 4 weeks before inclusion.
* The use of NSAIDs or other nephrotoxic drugs in the last 4 weeks before inclusion.
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:

* 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
D: 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

Answer: A