A Study Evaluating the Safety and Effectiveness of BIV201 and Standard of Care Compared to Standard of Care to Reduce the Recurrence of Ascites and Complications in Patients with Refractory Ascites Secondary to Decompensated Liver Cirrhosis

Overview

About this study

The purpose of this study is to evaluate the clinical effectiveness of BIV201 continuous infusion in addition to SOC compared to SOC alone in adult patients with refractory ascites secondary to decompensated hepatic cirrhosis.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Informed consent, or consent via legally authorized representative, if institutionally required for subjects with decompensated liver cirrhosis with current HE Grade 1 or 2, prior to any study-related procedures.
  • Male or female patients age ≥ 18 years old.
  • Cirrhosis of the liver.
  • Patient has diuretic-resistant ascites, intractable ascites, or in the opinion of the Investigator, is unsuitable for treatment with an effective dose of diuretics for other reasons.
  • Patients must have required in the 60-day period from the last LVP before consent, between 3 and 9 LVPs, including the last LVP on or before the day of consent.
  • Dates for all LVPs occurring 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 days period prior to the last LVPs before consent.
  • Serum creatinine (SCr) ≤ 2.00 mg/dL determined prior to randomization with value at randomization being less than 1.5 fold higher than value obtained at the screening visit.
  • 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 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.

Exclusion Criteria:

  • 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.
  • Platelet count ≤ 100,000/µL for the first eight patients enrolled. Eligibility of patients with a platelet count > 65,000 but < 100,000/µL should be confirmed with the Medical Monitor.
  • Current or recent (within 3 months of consent) renal dialysis.
  • Current or recent (within 1 month of consent) hepatic encephalopathy Grade 3 or 4 (WestHaven criteria).
  • 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 that has required a thoracentesis in the 7 days prior to randomization, or anticipated to require one within 7 days post-randomization, known pulmonary hypertension or a history of hepatopulmonary syndrome.
  • Current or recent treatment (within 7 days of randomization) with octreotide, midodrine, vasopressin, dopamine or other vasopressors.
  • Treatment with ACE inhibitors or ARBs 30 days prior to randomization.
  • 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 14 days prior to consent. If a patient develops SBP in the pretreatment period randomization cannot occur for a minimum of 10 days and documented resolution of SBP.
  • SBP at baseline visit (LVP -1).
  • Episode of gastrointestinal hemorrhage (non-variceal) within 28 days prior to consent.
  • Episode of bleeding esophageal varices 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 2 weeks before randomization
  • 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).
  • Patients, who in the judgement of the Investigator, have been excessive alcohol drinkers 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.
  • Recipient of renal or liver transplant.
  • Implanted alfapump or previous recipient of alfapump that had pump removed within past 3 months
  • 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.

Eligibility last updated 4/14/22.  Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Douglas Simonetto, M.D.

Open for enrollment

Contact information:

Amy Olofson R.N.

(507) 538-6547

Olofson.Amy@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Andrew Keaveny, M.D.

Open for enrollment

Contact information:

Robert Brannock B.S.

Brannock.Robert@mayo.edu

More information

Publications

Publications are currently not available
.

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