Title

Refractory Ascites in Patients With Liver Cirrhosis, and the Potential Treatment With 48 Hours Infusion of Ularitide.
Single-center, Randomized, Double-blind, Placebo-controlled Clinical Trial for the Safety, Tolerability and Efficacy of Ularitide in Cirrhosis Patients With Refractory Ascites.
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Status

    Recruiting
  • Intervention/Treatment

    Ularitide ...
  • Study Participants

    38
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.
The investigators hypothesize that ularitide infusion is more effective than placebo to induce and maintain clinically meaningful natriuresis and diuresis in patients with liver cirrhosis and refractory ascites.

Participants will be given ularitide or placebo intravenously while hospitalized at Department of Hepatology and Gastroenterology at Aarhus University Hospital. During the hospitalization blood and urine samples are frequently collected.

30 ng/kg/min is the starting dosage for all participants. Depending on effects and/or side effects, ULA04 is designed to individualize treatment doses by up- and/or downtitration of the infusion dose within a predefined dose range. Relevant safety precautions are incorporated in the study design and treatment will be prematurely discontinued if a pre-defined stopping criteria presents.

Patients will be followed up for the appearance of serious adverse events 30 days after the treatment.

If a separate written consent is given by the participants, additional blood and urine samples will be collected and stored in a biobank for future research.
Study Started
Aug 01
2020
Primary Completion
Jan 31
2023
Anticipated
Study Completion
Aug 31
2023
Anticipated
Last Update
May 25
2022

Drug Ularitide

Continuous intravenous infusion for 48 hours at a dose of 30 ng/kg/min. Depending on effect and/or side effects dose can be adjusted to 15 ng/kg/min or 45 ng/kg/min.

  • Other names: Urodilatin

Drug Placebo

Continuous intravenous infusion for 48 hours at a bodyweight-adjusted infusion rate.

Ularitide Experimental

Test product. Continuous intravenous infusion with 30 ng/kg/min for 48 hours.

Placebo Placebo Comparator

Matching placebo. Continuous IV infusion for 48 hours.

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
No Results Posted