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Cirrhosis, LiverPhase 2ULA04NCT04311489

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

A Phase 2 study testing Ularitide in people with Cirrhosis, Liver and Ascites Hepatic, run by University of Aarhus at 1 site in Denmark.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cirrhosis, Liver, Ascites Hepatic
What is being tested?
Ularitide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
17 participants
Where
1 siteDenmark
Study dates
1 Aug 2020to 30 Nov 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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)
Show all 21Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Department of Hepatology and Gastroenterology, Aarhus University Hospital

    Aarhus, Central Jutland, 8200

Other trials in Denmark

About this study

Official title: Single-center, Randomized, Double-blind, Placebo-controlled Clinical Trial for the Safety, Tolerability and Efficacy of Ularitide in Cirrhosis Patients With Refractory Ascites.

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.

Read the detailed description

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.

Being tested
Ularitide, Placebo
Keywords
Cirrhosis, Ascites, Refractory ascites, Natriuresis, Diuresis, Urodilatin, Ularitide, natriuretic peptide
Medical subject headings
Liver Cirrhosis, Fibrosis, Ascites

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • UlaritideDrug

    Also called Urodilatin

    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.

  • PlaceboDrug

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

Study groups in NCT04311489
Study groupRoleWhat they receive
UlaritideExperimentalTest product. Continuous intravenous infusion with 30 ng/kg/min for 48 hours.
Receives: Drug: Ularitide
PlaceboPlacebo comparatorMatching placebo. Continuous IV infusion for 48 hours.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute and relative change in sodium excretion rate.

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

  2. Absolute and relative change in urine volume.

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

  3. Change of absolute body weight.

    Measured: At termination of treatment (up to 48 hours)

Secondary outcomes (14)

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

    Urine volume increase of ≥100 % versus baseline, urine volume increase ≥50 % versus baseline, natriuresis increase by ≥100 % versus baseline and/or body weight reduction by ≥2 kg versus baseline.

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

  2. Absolute and relative change in sodium excretion rate.

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

  3. Absolute and relative change in urine volume.

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

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

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

  5. Absolute and relative change in waist circumference.

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

  6. Absolute and relative change in serum creatinine.

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

  7. Absolute and relative change in estimated glomerular filtration rate (eGFR).

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

  8. Absolute and relative change in plasma and urine osmolalities.

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

  9. Absolute and relative change in GFR-24h-Crea (Glomerular filtration rate based on 24-hour creatinine clearance).

    Measured: After 24 hours and 48 hours of treatment

  10. Absolute and relative change in hematocrit.

    Measured: After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up

  11. Absolute and relative change in plasma copeptin concentration.

    Measured: After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up

  12. Absolute and relative change in plasma renin concentration.

    Measured: After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up

  13. Absolute and relative change in plasma angiotensin concentration.

    Measured: After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up

  14. Absolute and relative change in plasma aldosterone concentration.

    Measured: After 24 hours and 48 hours of treatment and at 6 hours post-treatment follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2020
  2. Study start1 Aug 2020
  3. Primary completion30 Nov 2022
  4. Study completion30 Nov 2022

Why it stopped: Interim analysis showing safety concerns

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, double-blind, placebo-controlled clinical trial
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04311489
Sponsor's protocol ID
ULA04
Other IDs
2019-002268-28, 2019
Acronym
ULA04
Status last verified
May 2022
First submitted
12 Mar 2020
Last updated
18 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 9697672

  • 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.

    PubMed 17257428

  • 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.

    PubMed 34851251

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ularitide in people with Cirrhosis, Liver and Ascites Hepatic, run by University of Aarhus at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Interim analysis showing safety concerns). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute and relative change in sodium excretion rate. (time frame: After 24 hours and at termination of treatment (up to 48 hours)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04311489, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2023.

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