Please select the eligibility criteria that correspond to the clinical trial below.
Title: Midodrine and Albumin for Cirrhotic Patients in the Waiting List for Liver Transplantation
Brief Summary: The aim of this study is to evaluate the effect of prolonged administration of albumin and midodrine on the prevention of complications (renal failure, sepsis, hemorrhage, hepatic encephalopathy and hyponatremia) in patients with cirrhosis in the waiting list for liver transplantation. One hundred and ninety four patients with cirrhosis and awaiting a liver transplantation will include in the study. Patients will be randomized to receive albumin and midodrine (treatment group) or administration of placebo (saline for albumine) and tablets with excipients without midodrine (control group). Patients will be followed-up during 12th months. In the treatment group albumin will be given at a dose of 40g every 15 days and midodrine 5mg tid, in addition with lactitol (conventional doses) and the specific treatment that patients require by cirrhosis. The group control will receive placebo in the same way than the treatment group in addition with lactitol and the specific treatment that they require by their disease. In all the patients liver and renal function test, hormones determination (renin, aldosterone, noradrenaline), and cytokines will be determined in basal conditions. All these determinations will be repeated at month 1st,3rd, 6th and 12th months. Before the inclusion in the study neuropsychological test and critical flicker test will be performed to diagnose minimum EH. These tests will be repeated at 3rd, 6th and 12th months. All the determinations will be repeated at any time that the patients develop any complication considered as an end point. In baseline conditions and at 3rd and 6th months a questionnaire of quality of life (SF36) will be performed. During a year of follow-up the number of paracentesis that patients require, the incidence of renal failure and EH and their relationship with hormonal activity and cytokine levels, free transplant survival and quality of life will be recorded.


Options:
A: 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
B: 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
C: Inclusion Criteria:

1. Males and non-pregnant females (determined by serum pregnancy test) ≥ 18 years of age. Women of childbearing age must be prepared to use at least 1 effective (≤ 1% failure rate) method of contraception during the course of the study
2. Cirrhosis of the liver defined by histological and/or clinical, and/or radiological criteria
3. Presenting refractory or recurrent ascites and requiring periodic large volume paracentesis (large volume defined as \> 5 L to accord with teh clinical guidance of EASL, European Association for the Study of the Liver, which recommends withdrawal of 5 L should precipitate administration of albumin).
4. Capable of giving written informed consent, willing to comply with study procedures and ability to operate the device

Exclusion Criteria:

1. Gastrointestinal haemorrhage over the last 7 days
2. Renal failure defined as serum creatinine higher than or equal to 2 mg/dl
3. Severe coagulopathy defined as prothrombin time greater than 40% more than upper limit of Normal (as determined locally).
4. Platelet count of less than 40000 /uL unless platelet therapy is given at the time of surgery
5. Clinical Evidence of recurring bacterial peritonitis, defined as 2 or more episodes over the last 6 months or a single episode within the last 2 weeks.
6. Clinical evidence of recurring urinary infections, defined as 2 or more episodes over the last 6 months or a single episode within the last 2 weeks.
7. Clinical evidence of loculated ascites.
8. Advanced hepatocarcinoma, defined as one which exceeds Milan criteria.
9. Obstructive uropathy, residual urinary volume exceeding 100 ml, or any bladder anomaly which might contraindicate implantation of the device.
10. Concurrently implanted with any other Active Implantable Medical Device, including, but not limited to, cardiac pacemaker or cardioverter defibrillator.
11. Pregnant females or females anticipating pregnancy during study period
12. Patients currently enrolled in another interventional clinical study
13. Other concomitant disease or condition likely to significantly decrease life expectancy or present anaesthetic risk (e.g., moderate to severe congestive heart failure)
14. Known presence of human immunodeficiency virus (HIV)
15. Immuno-modulatory treatment (including azothioprine, methotrexate, anti-TNF therapies) used within last 4 months
16. Known or suspected hepatic or extra hepatic malignancy, unless adequately treated or in complete remission for ≥ 3 years
17. BMI \> 40 presenting a risk for surgery and tunneled lines
18. Patients with contraindications for general anesthesia
D: Inclusion Criteria:60 consecutive patients with cirrhosis and refractory or recurrent ascites with stable renal function ( creatinine level \<1.5mg/dl for at least 7 days ).

Exclusion Criteria:

* Presence of gastrointestinal bleeding, HRS, hepatic encephalopathy of grade 2 or higher or infection within 1 month preceding the study or during the study, presence of diabetes, intrinsic renal or cardiovascular disease or arterial hypertension on history and physical examination, abnormal urine analysis, chest radiograph or electrocardiogram, presence of hepatocellular carcinoma or portal vein thrombosis or treatment with drugs with known effects on systemic and renal hemodynamics within 7 days of inclusion .

Answer: A