Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

Phase 2

Completed

Conditions: Cirrhosis
Ascites Hepatic

Interventions: Drug: Terlipressin acetate continuous infusion

Registration Number: NCT03107091

Lead Sponsor: BioVie Inc.

Brief Summary: Low-dose continuous infusion of terlipressin will be administered to six cirrhotic patients with refractory ascites.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Terlipressin acetate continuous infusion	Terlipressin acetate continuous infusion	Continuous infusion of terlipressin starting at 2 mg/day over 7 days in-house and if tolerated continue treatment in the ambulatory setting for 21 days

Primary Outcome Measures

Name	Time	Method
Steady State Plasma Levels of Terlipressin and 8-lysine Vasopressin During Terlipressin Continuous Infusion at 2 mg/Day in Cirrhotic Patients With Refractory Ascites	7 day treatment	Serial sampling for determination of Terlipressin concentration and metabolite 8-lysine vasopressin in plasma at steady state (Css)
Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites	28 day treatment period and 28 day post-treatment	Rate of treatment emergent adverse events assessed by physical examination and laboratory safety

Secondary Outcome Measures

Name	Time	Method
Change in Requirement of Large Volume Paracentesis With Continuous Infusion of Terlipressin	28 day post-treatment	Comparison of pre-treatment and post-treatment incidence of therapeutic paracentesis and change in volume of ascites removed