Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

Terlipressin continuous infusion will be adminstered via an ambulatory pump initially for 7
days in a clinical pharmacology unit. Serial blood draws for pharmacokinetic analysis will be
performed to determine steady state concentration of both terlipressin and
8-lysine-vasopressin during infusion. After establishing safety and tolerance of infusion for
7 days, patients will be transitioned to an outpatient setting where they will be treated
with terlipressin continuous infusion for an additional 21 days, monitored daily by home care
nurses.

A total of 6 patients will be treated. Monitoring will include successful management of
ascites, with reduction in paracentesis procedures and decreased ascites fluid volume,
further supported by improvement in renal function.

Inclusion Criteria:

- Patients with cirrhosis and refractory ascites who required 3 or more large volume (4
liters and more) paracenteses in the previous 60 days

Exclusion Criteria:

- Ascites with causes other than cirrhosis such as nephrogenic ascites or malignant
ascites due to peritoneal carcinomatosis

- Total bilirubin > 5 mg/dL

- Blood clotting International normalized ratio (INR) > 2.5

- Serum creatinine > 2.0 mg/dL

- Current or recent (within 3 months of consent) renal dialysis

- Hepatic encephalopathy grade 3 or 4

- 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)

- Current or recent treatment (within 7 days) with octreotide, midodrine, vasopressin,
dopamine or other vasopressors

- Respiratory failure requiring positive airway pressure devices or intubation

- SIRS/sepsis episode in the previous 28 days from consent

- Episode of spontaneous bacterial peritonitis or gastrointestinal hemorrhage within 28
days of consent

- Ongoing documented or suspected infection

- Severe cardiovascular disease that are contraindication to terlipressin therapy such
as advanced arteriosclerosis, arrhythmia, coronary insufficiency or uncontrolled
hypertension

- Findings suggestive of organic renal disease (severe proteinuria/hematuria, or
abnormal renal ultrasound suggestive of obstructive or other renal pathology)

- Severe comorbidity that in the opinion of the Investigator would affect short-term
prognosis and/or disallow safe participation in the trial (such as for example, severe
anemia or pancytopenia, advanced neoplasia, hepatocellular carcinoma [confirmed with
serum alpha1-fetoprotein testing], severe chronic obstructive pulmonary disease or
asthma)

- Alcoholics who have not been abstinent for the past 6 months

- Transjugular intrahepatic portosystemic shunt or other surgical shunt

- For female patients: Confirmed pregnancy

- Known allergy or hypersensitivity to terlipressin

- Participation in other clinical research studies involving the evaluation of other
investigational drugs or devices within 30 days of consent.