continuous infusion terlipressin for patients with cirrhosis and refractory ascites

Conditions: Cirrhosis; Ascites Hepatic

Summary: low-dose continuous infusion of terlipressin will be administered to six cirrhotic patients with 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.

Eligibility criteria:
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.

Keywords: terlipressin terlipressin acetate