AscitesPhase 2NCT04112199
A Study for Evaluation of BIV201 to Reduce Ascites and Complications in Patients With Cirrhosis and Refractory Ascites
A Phase 2 study testing BIV201 continuous infusion in people with Ascites and Decompensated Cirrhosis, run by BioVie Inc. at 10 sites in United States.
Trial summary
This study evaluates the addition of BIV201 (terlipressin diacetate) as a continuous infusion in addition to standard of care (diuretics and therapeutic paracentesis) for reduction of ascites and complications in adult patients with refractory ascites secondary to decompensated cirrhosis Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ascites, Decompensated Cirrhosis
- What is being tested?
- BIV201 continuous infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 10 sitesUnited States
- Study dates
- 17 Jun 2021to 8 May 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent prior to any study-related procedures
- Male or female patients age 18 to 75 years old
- Cirrhosis of the liver (Non-alcoholic steatohepatitis, alcohol, viral and autoimmune)
- Patient has diuretic-resistant, intractable ascites or is unsuitable for treatment with diuretics and required:
- o In the 60-day period from the last LVP before consent, required, between 3 and 9 LVPs, including the last LVP on or before the day of consent.
- Dates for all LVPs that occurred within 90 days prior to consent have been recorded. The volume of ascites removed at each of the LVPs must also have been recorded for the 90-day period prior to the last LVPs before consent
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- Serum creatinine (SCr) ≤2.00 mg/dL determined prior to randomization
- Women of child-bearing potential (e.g. not post-menopausal for at least one year or surgically sterile) must be neither pregnant nor lactating and must agree to use adequate birth control or be abstinent for the duration of the study
- If patient is treated with ACE inhibitors or beta blockers, dose has been stable for at least 30 days prior to randomization and may be maintained on that dose for the trial duration
- If patient is treated with diuretics, patient has been on a stable daily dose for at least 10 days prior to consent
- Willing and able to comply with trial instructions
Who cannot join
- Ascites with causes other than cirrhosis; such as cardiac or nephrogenic ascites or malignant ascites due to peritoneal carcinomatosis
- Urinary sodium excretion >100 mmol/day between day of consent and randomization
- Total bilirubin >5 mg/dL
- Blood clotting International normalized ratio (INR) >2.5
- Current or recent (within 3 months of consent) renal replacement therapy
- Current or recent (within 3 month of consent) hepatic encephalopathy Grade 3 or 4 (West-Haven)
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- Superimposed acute liver failure/injury due to factors including acute alcoholic hepatitis, acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom [Amanita] poisoning)
- History or presence of hepatic hydrothorax, known pulmonary hypertension and a history of hepatopulmonary syndrome
- Current or recent treatment (within 7 days of randomization) with octreotide, midodrine, vasopressin, dopamine or other vasopressors
- Current or recent (in the previous 60 days from consent) episode of respiratory failure requiring positive airway pressure (PAP) devices or intubation
- Sepsis episode in the previous 28 days from consent
- Episode of SBP within the 28 days prior to consent
- Episode of gastrointestinal hemorrhage (non-variceal) within 28 days prior to consent
- Episode of esophageal variceal bleed within one week prior to consent
- Ongoing documented or suspected infection
- Severe cardiovascular disease that is a contraindication to terlipressin therapy such as a history of myocardial infarction, angina pectoris, advanced arteriosclerosis, uncontrolled cardiac arrhythmia, severe coronary insufficiency or uncontrolled hypertension
- Findings suggestive of severe organic renal disease (severe proteinuria/hematuria, or abnormal renal ultrasound suggestive of obstructive renal pathology)
- Use of nephrotoxic drugs (e.g., aminoglycosides) in the 4 weeks before screening
- 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 progressive neoplasia such as hepatocellular carcinoma, unless eligible for transplant)
- Patient who, in the judgment of the investigator, has been an excessive alcohol drinker in the past 12 weeks
- Patient is in the opinion of the investigator, despite previous education on sodium restriction, anticipated to remain grossly non-compliant of sodium restricted diet
- Implanted alfapump or previous recipient of alfapump that had pump removed within past 3 months
- Recipient of renal or liver transplant
- Planned elective surgery related to cirrhosis complications, for example for hernia repair
- Known allergy or hypersensitivity to terlipressin
- Participation in other clinical research studies involving the treatment with other investigational drugs or evaluation with implantable devices within 30 days of consent
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Mercy Medical Center
Baltimore, Maryland, 21202
Medical University of South Carolina
Charleston, South Carolina, 29425
Indiana University
Indianapolis, Indiana, 46202
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
UCLA
Los Angeles, California, 90095
University of Miami
Miami, Florida, 33136
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Hunter Holmes McGuire Veterans Affairs Medical Center
Richmond, Virginia, 23249
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: A Phase 2 Randomized, Dose-Titration, Open-Label Study Evaluating the Safety and Efficacy of BIV201 Compared to Standard of Care to Reduce Ascites and Complications in Cirrhotic Patients With Refractory Ascites
This study evaluates the addition of BIV201 (terlipressin diacetate) as a continuous infusion in addition to standard of care (diuretics and therapeutic paracentesis) for reduction of ascites and complications in adult patients with refractory ascites secondary to decompensated cirrhosis
Read the detailed description
Terlipressin has been shown to reduce portal hypertension, improve renal function and induce natriuresis in cirrhotic patients with ascites without hepatorenal syndrome (HRS). It is approved in Europe for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered as an IV bolus starting at 1 mg every 6 h and increased to 2 mg every 6 h (maximum 8 mg/day depending on response).
This study will evaluate the use of terlipressin delivered by continuous infusion for two 28 day treatment cycles for reduction of ascites accumulation and complications in adult patients with refractory ascites secondary to decompensated cirrhosis. Continuous infusion allows for a significant reduction in the daily effective dose required for treatment and improved safety of terlipressin delivered as a low-dose continuous infusion could enable its use in the outpatient setting in the prolonged treatment of patients with refractory ascites.
- Conditions
- Ascites, Decompensated Cirrhosis
- Being tested
- BIV201 continuous infusion
- Keywords
- Terlipressin, Refractory ascites
- Medical subject headings
- Ascites
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIV201 continuous infusionDrug
Also called terlipressin diacetate
BIV201 continuous infusion with terlipressin for a total of two 28 day cycles. Initiate treatment at 3 mg per 24 hour period and titrate stepwise up to a maximum of 8 mg per 24 hour period based on tolerability and response.
| Study group | Role | What they receive |
|---|---|---|
| BIV201 plus Standard of Care | Experimental | BIV201 continuous infusion - treatment for two 28 day cycles. Receives: Drug: BIV201 continuous infusion |
| Standard of care | No intervention | Per AASLD guidelines: diuretics and therapeutic paracentesis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of complications, at least grade 2 severity
Incidence of complications, at least grade 2, during the 180 days following randomization
Measured: 180 days following randomization
Secondary outcomes (1)
Change in cumulative ascites
Change in cumulative ascites during the first 12 weeks following randomization versus the 12 weeks pre-treatment
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start17 Jun 2021
- Primary completion8 May 2023
- Study completion8 May 2023
Why it stopped: For reasons unrelated to safety or efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AscitesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Thirty patients will be randomized to either BIV201 continuous infusion plus SOC or SOC alone.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioVie Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joseph Palumbo, MD, Study director, BioVie Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112199
- Sponsor's protocol ID
- CIT-002
- Status last verified
- May 2024
- First submitted
- 30 Sep 2019
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified individual participant data for primary and secondary end-points may be made available after NDA filing.
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Dose-Titration, Open-Label Study Evaluating the Safety and Efficacy of BIV201 Compared to Standard of Care to Reduce Ascites and Complications in Cirrhotic Patients With Refractory Ascites
- ClinicalTrials.gov ID
- NCT04112199
- Acronym / sponsor ID
- CIT-002
- Conditions
- Ascites, Decompensated Cirrhosis
- Keywords
- Terlipressin, Refractory ascites
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: For reasons unrelated to safety or efficacy
- Enrolment
- 15 participants (actual)
- Lead sponsor
- BioVie Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jun 2021 (actual)
- Primary completion
- 8 May 2023 (actual)
- Study completion
- 8 May 2023 (actual)
- First posted
- 2 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the addition of BIV201 (terlipressin diacetate) as a continuous infusion in addition to standard of care (diuretics and therapeutic paracentesis) for reduction of ascites and complications in adult patients with refractory ascites secondary to decompensated cirrhosis
Detailed description
Terlipressin has been shown to reduce portal hypertension, improve renal function and induce natriuresis in cirrhotic patients with ascites without hepatorenal syndrome (HRS). It is approved in Europe for the treatment of bleeding esophageal varices and HRS type 1 and is usually administered as an IV bolus starting at 1 mg every 6 h and increased to 2 mg every 6 h (maximum 8 mg/day depending on response).
This study will evaluate the use of terlipressin delivered by continuous infusion for two 28 day treatment cycles for reduction of ascites accumulation and complications in adult patients with refractory ascites secondary to decompensated cirrhosis. Continuous infusion allows for a significant reduction in the daily effective dose required for treatment and improved safety of terlipressin delivered as a low-dose continuous infusion could enable its use in the outpatient setting in the prolonged treatment of patients with refractory ascites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Thirty patients will be randomized to either BIV201 continuous infusion plus SOC or SOC alone.
| Arm | Type | Receives |
|---|---|---|
| BIV201 plus Standard of Care | Experimental | Drug: BIV201 continuous infusionBIV201 continuous infusion - treatment for two 28 day cycles. |
| Standard of care | No intervention | –Per AASLD guidelines: diuretics and therapeutic paracentesis |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Informed consent prior to any study-related procedures
- Male or female patients age 18 to 75 years old
- Cirrhosis of the liver (Non-alcoholic steatohepatitis, alcohol, viral and autoimmune)
- Patient has diuretic-resistant, intractable ascites or is unsuitable for treatment with diuretics and required:
- o In the 60-day period from the last LVP before consent, required, between 3 and 9 LVPs, including the last LVP on or before the day of consent.
Key exclusion criteria (26 listed)
- Ascites with causes other than cirrhosis; such as cardiac or nephrogenic ascites or malignant ascites due to peritoneal carcinomatosis
- Urinary sodium excretion >100 mmol/day between day of consent and randomization
- Total bilirubin >5 mg/dL
- Blood clotting International normalized ratio (INR) >2.5
- Current or recent (within 3 months of consent) renal replacement therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIV201 continuous infusionAlso: terlipressin diacetateBIV201 continuous infusion with terlipressin for a total of two 28 day cycles. Initiate treatment at 3 mg per 24 hour period and titrate stepwise up to a maximum of 8 mg per 24 hour period based on tolerability and response. | Drug | BIV201 plus Standard of Care |
Primary outcome
Incidence of complications, at least grade 2 severity
Time frame: 180 days following randomization
Incidence of complications, at least grade 2, during the 180 days following randomization
1 secondary outcome
Change in cumulative ascites
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: For reasons unrelated to safety or efficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Individual participant dataSharing planned: No. De-identified individual participant data for primary and secondary end-points may be made available after NDA filing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Palumbo, MD study director
BioVie Inc.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BIV201 continuous infusion in people with Ascites and Decompensated Cirrhosis, run by BioVie Inc. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: For reasons unrelated to safety or efficacy). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of complications, at least grade 2 severity (time frame: 180 days following randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.