Clinical trial NCT03107091: Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cirrhosis
Ascites Hepatic
Keywords: Terlipressin
Terlipressin acetate
Lead sponsor: BioVie Inc.
Sponsor class: INDUSTRY
First posted: 2017-04-11
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label prospective study in a cohort of 6 patients
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites
timeFrame: 28 day treatment period and 28 day post-treatment
measure: Steady State Plasma Levels of Terlipressin and 8-lysine Vasopressin During Terlipressin Continuous Infusion at 2 mg/Day in Cirrhotic Patients With Refractory Ascites
timeFrame: 7 day treatment
Secondary outcomes:
measure: Change in Requirement of Large Volume Paracentesis With Continuous Infusion of Terlipressin
timeFrame: 28 day post-treatment
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
Study officials:
affiliation: BioVie Inc.
name: Patrick Yeramian, MD
role: STUDY_DIRECTOR
References: