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

NCT04311489 | Terminated Phase 2 DMC

• 2 other identifiers: ULA042019-002268-28
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cirrhosis, Liver; Ascites Hepatic

Keywords

Cirrhosis; Ascites; Refractory ascites; Natriuresis; Diuresis; Urodilatin; Ularitide; natriuretic peptide

Outcome Measures

Primary Outcomes (3)

• Absolute and relative change in sodium excretion rate.

  After 24 hours and at termination of treatment (up to 48 hours)

• Absolute and relative change in urine volume.

  After 24 hours and at termination of treatment (up to 48 hours)

• Change of absolute body weight.

  At termination of treatment (up to 48 hours)

Secondary Outcomes (14)

• Number of responders in the ularitide group versus the placebo group, defined by:

  Throughout the treatment period. Latest measure at termination of treatment (up to 48 hours)

• Absolute and relative change in sodium excretion rate.

  After 2 hours and 4 hours of treatment and at 6 hours post-treatment follow-up

• Absolute and relative change in urine volume.

  After 2 hours and 4 hours of treatment and at 6 hours post-treatment follow-up

• Absolute and relative change in plasma cyclic guanosine monophosphate (cGMP) concentration.

  Throughout the treatment period. Latest measure at 6 hours post-treatment follow-up

• Absolute and relative change in waist circumference.

  After 24 hours and at termination of treatment (up to 48 hours)

Other Outcomes (4)

• Incidence of adverse events/reactions.

  Throughout the treatment period and until 6 hours post-treatment follow-up

• Incidence of serious adverse events/reactions.

  Throughout the treatment period and until 30 days post-treatment follow-up

• Incidence of stopping criteria leading to a dose reduction.

  Throughout the treatment period (up to 48 hours)

Study Arms (2)

Ularitide

EXPERIMENTAL

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

Drug: Ularitide

Placebo

PLACEBO COMPARATOR

Matching placebo. Continuous IV infusion for 48 hours.

Drug: Placebo

Interventions

Ularitide DRUG

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.

Also known as: Urodilatin

Ularitide

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Proteinuria \>500 mg/day
• Hemoglobin \<5.5 mmol/L
• 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
• Fertile women not using contraception, either an intrauterine device or hormonal contraception
• Positive pregnancy test in pre-menopausal women or in breast-feeding women
• Legal incapacity or limited legal capacity

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• ADS AIPHIA Development Services AG: collaborator

Study Sites (1)

Department of Hepatology and Gastroenterology, Aarhus University Hospital

Aarhus, Central Jutland, 8200, Denmark

Location

Related Publications (3)

• Carstens J, Greisen J, Jensen KT, Vilstrup H, Pedersen EB. Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites. J Am Soc Nephrol. 1998 Aug;9(8):1489-98. doi: 10.1681/ASN.V981489.

  PMID: 9697672 BACKGROUND

• Carstens J, Gronbaek H, Larsen HK, Pedersen EB, Vilstrup H. Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention. BMC Gastroenterol. 2007 Jan 26;7:1. doi: 10.1186/1471-230X-7-1.

  PMID: 17257428 BACKGROUND

• Gantzel RH, Meyer M, Mazgareanu S, Aagaard NK, Jepsen P, Holzmeister J, Watson H, Gronbaek H. Ularitide as treatment of refractory ascites in cirrhosis- a study protocol for a randomised trial. Dan Med J. 2021 Nov 12;68(12):A07210610.

  PMID: 34851251 BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis; Fibrosis; Ascites

Interventions

Ularitide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Henning Grønbæk, Prof,MD,PhD

  Department of Hepatology and Gastroenterology, Aarhus University Hospital,

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled clinical trial

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 17, 2020
• Study Start: August 1, 2020
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: May 18, 2023

Record last verified: 2022-05

Locations

DK (1)