Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide.

• Status: Recruiting
• Trial end date: 2023-08-31
• Target enrollment: 0
• Participant gender: All

Summary

This clinical trial intends to investigate the safety, tolerability and efficacy of ularitide on the renal response in patients with liver cirrhosis and refractory ascites for a maximum exposure duration of 48 hours, through a randomized, placebo-controlled, double-blind, single-center trial.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; ADS AIPHIA Development Services AG
• Treatments: Ularitide

Criteria

Inclusion Criteria:

• Men and women >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 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 <60 mmol/24 hour

• Serum creatinine <150 µmol/L

• Child-Turcotte-Pugh score of B or C (<13)

• Bilirubin <150 µmol/L

• Prothrombin time (PP) 0.20-0.60 (INR 1.3-2.5)

• Systolic blood pressure ≥95 mmHg

• Written informed consent to participate in the clinical trial

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

• Positive pregnancy test in pre-menopausal women or in breast-feeding women

• 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