TITLE: Alfapump® system in the treatment of refractory or recurrent ascites: a multicenter single arm non-randomized within subject crossover design pivotal study
SPONSOR: Sequana Medical
Primary Investigator: Dr. Reddy
CONTACT: Maggie Harte ( Maggie.Harte@Pennmedicine.upenn.edu)
TITLE: A Phase 2 Randomized, Controlled, Dose-titration, Open-Label Study Evaluating the Safety and Efficacy of BIV201 in Addition to 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
SPONSOR: Biovie Inc.
Primary Investigator: Dr. Reddy
CONTACT: Grace Kim-Lee (GraceKim.Lee@pennmedicine.upenn.edu)
Criteria
Inclusion Criteria
- 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:
- 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
- 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
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
- 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)
- 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