Liver cirrhosis with refractory ascites. MedDRA version: 20.0 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 100000004871 MedDRA version: 20.0 Level: PT Classification code 10003445 Term: Ascites System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: Ularitide
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: ULARITIDE
CAS Number: 118812-69-4
Current Sponsor code: Ularitide
Concentration unit: mg millig
Sponsors
Department of Hepatology and Gastroenterology, Aarhus University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age > 18 years - Liver cirrhosis confirmed by fibroscan (>20 kPa), or by imaging with signs of an irregular liver surface with collaterals, or clinically by cirrhosis stigmata - Refractory ascites: Definition: failure to respond to or intolerance to high dose diuretics (spironolactone up to 400mg/day and furosemide up to 160mg/day) and/or early ascites recurrence (reappearance of grade 2 or 3 ascites within 4 weeks of initial mobilization or =2 paracentesis within last 3 months) - Urine sodium excretion =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Gastrointestinal bleeding within 2 weeks prior to inclusion - Proteinuria >500 mg/day - Hemoglobin <5.5 mmol/L - Spontaneous bacterial peritonitis within 2 weeks prior to inclusion - Loculated ascites - Hepatic encephalopathy grade 2-4 (West-Haven classification) - Obstructive uropathy - Primary kidney disease - Known diagnosis of congestive heart failure - Known diagnosis of acute-on-chronic liver failure - Known diagnosis of systemic inflammatory response syndrome - Acute infections by known diagnosis and/or antibiotic treatment - Known HIV infection - Known allergy to the investigational drug or other natriuretic peptides - Treatment with dobutamine, levosimendan, milrinone, any phosphodiesterase inhibitor, octreotide, midodrine, vasopressin, dopamine or other vasopressors within 2 weeks prior to inclusion - Nephrotoxic drugs within 1 month prior to inclusion - Fertile women not using contraception, either an intrauterine device or hormonal contraception (tablets, implants, transdermal patches, vaginal rings and injections) - Positive pregnancy test in pre-menopausal women or in breast-feeding women. Menopause is defined as no menses since =12 months prior to screening - Participation in an interventional clinical drug trial within 1 month prior to inclusion - Legal incapacity or limited legal capacity - Patients who are employees or relatives of the investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety, tolerability and efficacy of ularitide on the renal response in patients with liver cirrhosis and refractory ascites (as defined in this protocol) for a maximum exposure duration of 48 hours, through a randomized, placebo-controlled, double-blind, single-center clinical trial.;Secondary Objective: Not applicable;Primary end point(s): Change (absolute and relative) in sodium excretion rate at 24 hours post infusion start and at the end of treatment versus baseline. Change (absolute and relative) in urine volume at 24 hours post infusion start and at the end of treatment versus baseline. Change of absolute body weight at the end of treatment versus baseline.;Timepoint(s) of evaluation of this end point: To evaluate the parameters above: Urine samples are collected at baseline, after 24 hours of infusion and at the end of treatment. Body weight is measured at baseline and at the end of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Number of responders in the ularitide group versus the placebo group at the end of treatment as defined by: urine volume increase of =100 % versus baseline at 2 hours post treatment start or, urine volume increase of =50 % versus baseline at 24 hours post treatment start or, natriuresis increase at the end of treatment by 100 % versus baseline and/or bodyweight reduction by =2 kg at the end of treatment versus baseline. - Change (absolute and relative) in sodium excretion rate at 2 and 4 hours post infusion start and at 4 hours after the end of treatment. - Change (absolute and relative) in urine volume at 2 and 4 hours post infusion start and at 4 hours after the end of treatment versus baseline. - Change (absolute and relative) in serum creatinine at 24 hours post infusion start and at the end of treatment versus baseline. - Change (absolute and relative) in waist circumference at 24 hours post infusion start and at the end of treatment versus baseline. - Change (absolute and relative) in urine osmolality at 24 hours post infusion start, at the end of treatment and at 4 hours after the end of treatment versus baseline. - Change (absolute and relative) in plasma osmolality at 24 hours post infusion start, at the end of treatment and at 4 hours after the end of treatment versus baseline. - Change (absolute and relative) in plasma copeptin concentration at 2, 24 hours post infusion start, at the end of treatment and at 4 hours after the end of treatment versus baseline. - Change (absolute and relative) in hematocrit at 24 hours post infusion start, at the end of treatment and at 4 hours after the end of treatment versus baseline. - Change (absolute and relative) in plasma cGMP concentration at 2, 24 hours post infusion start, at the end of treatment and at 4 hours after the end of treatment versus baseline. - Change (absolute and relative) in plasma aquaporin concentration at 2, 24 hours post infusion start, at the end of treatment and at 4 | — |
Countries
Denmark
Contacts
Public ContactClinical Trials Information
Department of Hepatology and Gastroenterology, Aarhus University Hospital
Outcome results
None listed