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Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

Primary Purpose

Cirrhosis, Ascites Hepatic

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Terlipressin acetate continuous infusion

About this trial

This is an interventional treatment trial for Cirrhosis focused on measuring Terlipressin, Terlipressin acetate

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Hunter Holmes McGuire VA Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Terlipressin acetate continuous infusion

Arm 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

Outcomes

Primary Outcome Measures

Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites

Rate of treatment emergent adverse events assessed by physical examination and laboratory safety

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)

Secondary Outcome Measures

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

Full Information

NCT ID

NCT03107091

First Posted

November 20, 2016

Last Updated

June 22, 2021

Sponsor

BioVie Inc.

1. Study Identification

Unique Protocol Identification Number

NCT03107091

Brief Title

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

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

July 15, 2017 (Actual)

Primary Completion Date

April 1, 2019 (Actual)

Study Completion Date

April 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

BioVie Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cirrhosis, Ascites Hepatic

Keywords

Terlipressin, Terlipressin acetate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Open label prospective study in a cohort of 6 patients

Masking

None (Open Label)

Masking Description

Open label

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Terlipressin acetate continuous infusion

Arm Type

Experimental

Arm 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

Intervention Type

Drug

Intervention Name(s)

Terlipressin acetate continuous infusion

Other Intervention Name(s)

Terlipressin

Intervention Description

Low-dose continuous infusion of Terlipressin administered via ambulatory pump over 28 days

Primary Outcome Measure Information:

Title

Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites

Description

Rate of treatment emergent adverse events assessed by physical examination and laboratory safety

Time Frame

28 day treatment period and 28 day post-treatment

Title

Steady State Plasma Levels of Terlipressin and 8-lysine Vasopressin During Terlipressin Continuous Infusion at 2 mg/Day in Cirrhotic Patients With Refractory Ascites

Description

Serial sampling for determination of Terlipressin concentration and metabolite 8-lysine vasopressin in plasma at steady state (Css)

Time Frame

7 day treatment

Secondary Outcome Measure Information:

Title

Change in Requirement of Large Volume Paracentesis With Continuous Infusion of Terlipressin

Description

Comparison of pre-treatment and post-treatment incidence of therapeutic paracentesis and change in volume of ascites removed

Time Frame

28 day post-treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Patrick Yeramian, MD

Organizational Affiliation

BioVie Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Hunter Holmes McGuire VA Medical Center

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23239

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Continuous Infusion Terlipressin for Patients With Cirrhosis and Refractory Ascites

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