Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

BioVie

Status and phase: Completed; Phase 2

Conditions: Cirrhosis; Ascites Hepatic

Treatments: Drug: Terlipressin acetate continuous infusion

Study type: Interventional

Funder types: Industry

Identifiers

NCT03107091

CIT-001

Details and patient eligibility

About

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

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Terlipressin acetate continuous infusion

Experimental group

Description:

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

Treatment:

Drug: Terlipressin acetate continuous infusion