Ascites Hepatic, Cirrhosis
Conditions
Keywords
Terlipressin, Terlipressin acetate
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.
Interventions
DRUGTerlipressin acetate continuous infusion
Low-dose continuous infusion of Terlipressin administered via ambulatory pump over 28 days
Sponsors
BioVie Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label
Intervention model description
Open label prospective study in a cohort of 6 patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
Single site
Participants by arm
| Arm | Count |
|---|---|
| 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
Terlipressin acetate continuous infusion: Low-dose continuous infusion of Terlipressin administered via ambulatory pump over 28 days | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Terlipressin Acetate Continuous Infusion |
|---|---|
| Age, Continuous | 61 years |
| Child-Pugh score | 9 score on a scale |
| MELD score | 15 score on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 participants |
| Serum creatinine | 1.30 mg/dL |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 3 / 6 |
| serious Total, serious adverse events | 4 / 6 |
Outcome results
Primary
Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites
Rate of treatment emergent adverse events assessed by physical examination and laboratory safety
Time frame: 28 day treatment period and 28 day post-treatment
Population: Enrolled
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | TEAE | 6 Participants |
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | Fatal TEAE | 0 Participants |
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | Serious AE | 4 Participants |
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | Related TEAE | 3 Participants |
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | Serious related TEAE | 0 Participants |
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | TEAE leading to drug withdrawal | 3 Participants |
| Terlipressin Acetate Continuous Infusion | Clinical Safety of Terlipressin Infusion in Cirrhotic Patients With Refractory Ascites | Grade 3 TEAE | 4 Participants |
Primary
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)
Time frame: 7 day treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Terlipressin Acetate Continuous Infusion | Steady State Plasma Levels of Terlipressin and 8-lysine Vasopressin During Terlipressin Continuous Infusion at 2 mg/Day in Cirrhotic Patients With Refractory Ascites | Terlipressin | 2.48 ng/mL |
| Terlipressin Acetate Continuous Infusion | Steady State Plasma Levels of Terlipressin and 8-lysine Vasopressin During Terlipressin Continuous Infusion at 2 mg/Day in Cirrhotic Patients With Refractory Ascites | 8-lysine vasopressin | 0.089 ng/mL |
Secondary
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
Time frame: 28 day post-treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Terlipressin Acetate Continuous Infusion | Change in Requirement of Large Volume Paracentesis With Continuous Infusion of Terlipressin | Percent change in volume ascites removed during 28d treatment period versus 28d pre-treatment period | -66.5 percent change |
| Terlipressin Acetate Continuous Infusion | Change in Requirement of Large Volume Paracentesis With Continuous Infusion of Terlipressin | Percent change in LVP interval during treatment versus before treatment | 128 percent change |