Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

Safety and Efficacy of Low-dose Terlipressin Delivered by Continuous Intravenous Infusion in Patients With Cirrhosis and Ascites Refractory to, or Intolerant of, Diuretic Therapy, Requiring Large Volume Paracentesis

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

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Ascites Hepatic
• Intervention / Treatment: Drug: Terlipressin acetate continuous infusion

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23239
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Terlipressin acetate continuous infusion; Low-dose continuous infusion of Terlipressin administered via ambulatory pump over 28 days; Other Names: Terlipressin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: BioVie Inc.
• Investigators: Study Director: Patrick Yeramian, MD, BioVie Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2017
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: November 20, 2016
• First Submitted That Met QC Criteria: April 4, 2017
• First Posted (Actual): April 11, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Terlipressin; Terlipressin acetate
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Ascites; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: CIT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No