Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-Center, Randomized, Placebo-controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 With Lucassin® (Terlipressin) (The REVERSE Study)
Brief Summary: This study is designed to evaluate the efficacy and safety of intravenous terlipressin versus placebo for the treatment of type 1 hepatorenal syndrome (HRS) in participants receiving standard of care albumin therapy.


Options:
A: Inclusion criteria

* Diagnosis of liver cirrhosis (based on clinical, laboratory, endoscopic and ultrasonographic features) and uncomplicated ascites according to the criteria of the International Ascites Club (1).
* Ongoing diuretic treatment with an anti-mineralocorticoid drug at a dose of 200 mg/day and furosemide of 25 mg/day, stable for at least 4 days prior enrollment, not inducing response (defined according to the criteria of the International Ascites Club as body weight reduction ≥ 800 grams in the 4 days prior enrollment). With this limitation, we aim to identify a fairly homogeneous population with a relatively advanced stage of the disease that will likely have more benefit from albumin administration, as also suggested by Gentilini at al. (17).
* Ongoing diuretic treatment with an anti-mineralocorticoid drug at a dose \> 200 mg/day and furosemide \> 25mg/day, independent of response to treatment.
* EGDS performed in the last 12 months, abdominal ultrasonography performed in the last 30 days, and laboratory tests required by the protocol in the last 7 days.

Exclusion criteria

* Age lower than 18 years
* No written informed consent
* Inability to follow written consent
* Established diagnosis of refractory ascites, as defined by the IAC (1)
* Need of 2 or more paracentesis during the last month
* Serum creatinine \> 1.5 mg/dl
* Organic nephropathy, as defined by the IAC (1)
* Hepatorenal syndrome type 1 in the last 15 days
* Gastrointestinal bleeding in the last 15 days
* Ongoing endoscopic eradication after a recent gastro-esophageal variceal bleeding
* Bacterial or fungal infection, including spontaneous bacterial peritonitis, in the last 7 days
* Hepatic encephalopathy grade III/IV
* Budd-Chiari Syndrome
* Patients with TIPS or other surgical porto-caval shunts
* Known and suspected active hepatocellular carcinoma or other malignancies
* Previous liver transplantation
* Ongoing alcohol abuse (patients should be abstinent for at least three months)
* Antiviral therapy for hepatitis B started in the last 6 months
* Heart failure
* Respiratory failure as defined as PO2 \<60 mmHg
* Known or suspected hypersensitivity to albumin
* Previous albumin administration given for the treatment of ascites in the last 30 days
* Patients enrolled in other clinical study for the treatment of ascites
* Use of experimental drugs for the last 2 months prior the inclusion in the present study
* Pregnancy and breast-feeding
* Females of child-bearing potential are excluded unless they meet one of the following criteria:

  * Post-menopausal for 6 months or more, and if post-menopausal for less than 2 years, a negative pregnancy test
  * Surgical sterilisation for more than one month duration and a negative pregnancy test
  * Intrauterine device in combination with a secondary barrier (e.g. diaphragm, condom or spermicide) and a negative pregnancy test
B: Inclusion Criteria:

All adult patients who

* Undergo resuscitation in the ICU
* AND fulfillment within the previous 24 hours of the criteria for severe sepsis (SCCM/ACCP)
* AND consent is obtainable either from the patient or by proxy (physician and/or next of kin)

Exclusion Criteria:

The following patients will not be evaluated for inclusion:

* Age \< 18 years old
* Previously randomised in the 6S trial
* Allergy towards hydroxyethyl starch or malic acid
* Treatment with \> 1000 ml's of any synthetic colloid within the last 24 hours prior to randomisation
* Any form of renal replacement therapy
* Acute burn injury \> 10% body surface area
* Severe hyperkalaemia, p-K \> 6 mM
* Liver or kidney transplantation during current hospital admission
* Intracranial bleeding within current hospitalisation
* Enrollment into another ICU trial of drugs with potential action on circulation, renal function or coagulation
* Withdrawal of active therapy
C: Inclusion Criteria:

1. Written informed consent by subject or legally authorized representative
2. At least 18 years of age
3. Cirrhosis and ascites
4. Rapidly progressive reduction in renal function characterized by:

   * Serum creatinine (SCr) ≥ 2.5 mg/dL
   * Doubling of SCr within 2 weeks (or for observations of shorter duration, SCr values over time meeting slope-based criteria for proportional increases likely to be representative of at least a doubling within 2 weeks
5. No sustained improvement in renal function (\< 20% decrease in SCr and SCr ≥ 2.25 mg/dL) 48 hours after both diuretic withdrawal and the beginning of plasma volume expansion with albumin:

Note: Albumin doses recommended by the International Ascites Club (IAC) are 1 g/kg on the first day (Maximum 100 g) and 20 - 40 g/day thereafter as clinically indicated. It is recommended (if clinically appropriate) that the albumin dose is kept constant during the study drug administration period.

Note: The qualifying SCr value is the SCr value at least 48 hrs after both diuretic withdrawal (if applicable) and the beginning of albumin fluid challenge. The qualifying SCr value must be ≥ 2.25 mg/dL AND at least 80% of the diagnostic (pre-fluid challenge) SCr value.

Exclusion Criteria:

1. SCr \> 7 mg/dL
2. Shock Note: Hypotension (Mean Arterial Pressure \< 70 mm Hg or a decrease \> 40 mm Hg in systolic blood pressure from baseline) with evidence of hypoperfusion abnormalities despite adequate fluid resuscitation.
3. Sepsis or systemic inflammatory response syndrome (SIRS)

   Note: SIRS: Presence of 2 or more of the following findings:

   Temperature \> 38°C or \< 36°C; heart rate \> 90/min; respiratory rate of \> 20/min or a PaCO2 of \< 32 mm Hg; white blood cell count of \> 12,000 cells/µL or \< 4,000/ µL.

   Note: Sepsis: Documented infection and systemic inflammatory response syndrome.
4. \< 2 days anti-infective therapy for documented or suspected infection
5. Proteinuria \> 500 mg/day
6. Hematuria or microhematuria (\> 50 red blood cells per high power field)
7. Clinically significant casts on urinalysis, including granular casts Note: Urine sediment examination is required to exclude presence of granular casts and other clinically significant casts \[e.g., red blood cell (RBC) casts\].
8. Evidence of intrinsic or parenchymal renal disease (including acute tubular necrosis)
9. Obstructive uropathy or other renal pathology on ultrasound or other medical imaging
10. Current or recent treatment (within 4 weeks) with nephrotoxic drugs, e.g., aminoglycosides, nonsteroidal anti-inflammatory drugs (NSAID) Note: Up to 3 doses of an NSAID within the prior month (prescription or over the counter) is acceptable Note: Use of short-term (\< 2 weeks) oral neomycin for acute encephalopathy is acceptable.
11. Current or recent (within 4 weeks) renal replacement therapy
12. Superimposed acute liver failure/injury due to factors other than alcoholic hepatitis, including acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom \[Amanita\] poisoning)
13. Current or recent treatment (within 48 hours) with octreotide, midodrine, vasopressin, dopamine or other vasopressors
14. Severe cardiovascular disease as judged by investigator
15. Estimated life expectancy of less than 3 days
16. Confirmed pregnancy
17. Known allergy or sensitivity to terlipressin or another component of the study treatment
18. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization
D: Inclusion Criteria:

* Patients with cirrhosis in the waiting list for liver transplant
* Patients with ascites or diuretic treatment
* To have written inform consent

Exclusion Criteria:

* Systolic blood pressure ≥150 mmHg and or diastolic blood pressure≥90 mmHg
* To have been treated with transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunts
* Antibiotic treatment in the previous week before the inclusion in the study
* Respiratory or cardiac failure
* HIV positive

Answer: C