Hepatorenal Syndrome
Conditions
Interventions
Terlipressin or matching placebo will be administered as an IV bolus injection over 2 minutes at an initial dose of 1 mg of terlipressin acetate (1 vial) q6h (plus-minus 30 minutes) (4 mg/day), up to
Sponsors
Taniguchi Tomohiro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provide informed consent (consent may be provided by the participant legally authorized representative). 2.Have Japanese heritage and be at least 18 years of age at time of consent. 3.Have a diagnosis of cirrhosis and ascites. 4.Have had an increase in SCr >=0.3 mg/dL within 48 hours or increase >=1.5 times baseline level (known or presumed to have occurred within previous 7 days), to a SCr of >=1.5 mg/dL (defined as AKI stage 1B or higher). 5.Have had no sustained improvement in renal function (defined as <20% decrease in SCr and SCr at least 1.5 mg/dL)48 hours after diuretic withdrawal and the beginning of plasma volume expansion with albumin.
Exclusion criteria
Exclusion criteria: 1.Has a SCr >4.0 mg/dL. 2.Has ACLF Grade 3. 3.Has pulse oximetric oxygen saturation (SpO2) on room air of =1 event of large volume paracentesis (LVP) of at least 4 L within 2 days of randomization. If >4 L are removed by paracentesis, the investigator must wait 48 hours prior to randomizing the participant. 6.Has used noradrenaline for 3 or more consecutive days within the 5-day screening/pretreatment period, or within 24 hours of randomization. Any vasopressor use must be stopped at least 24 hours prior to randomization. 7.Has a MELD Score of >=35. 8.Has sepsis or an uncontrolled bacterial infection (eg, persisting bacteremia, persisting ascitic fluid leukocytosis, fever, increasing leukocytosis with vasomotor instability). 9.Have a life expectancy of less than 30 days in the opinion of the investigator (eg, based on MELD, Child-Pugh etc). 10.Has had <2 days of anti-infective therapy for a documented or suspected infection. 11.Has shock 12.Has current or had recent (within 4 weeks) treatment with, or exposure to nephrotoxic agents (eg, aminoglycosides, amphotericin, cyclosporine A, cisplatin, nonsteroidal anti-inflammatory drugs [NSAIDs: eg, ibuprofen, naproxen, diclofenac], significant exposure to radiographic contrast agents [large doses or multiple injections of iodinated contrast media, eg, during coronary or abdominal angiogram] if a rise in SCr reasonably correlates with timing of exposure). 13.Has superimposed acute liver injury due to drugs (eg, acetaminophen), dietary supplements, herbal preparations, viral hepatitis, or toxins (eg, Amanita toxin with mushroom poisoning carbon tetrachloride), with the exception of acute alcoholic hepatitis. 14.Has evidence of intrinsic, or obstructive uropathy or parenchymal renal disease on ultrasound or other imaging. Such imaging should only be performed if indicated. 15.Has proteinuria greater than 500 mg/day. 16.Has tubular epithelial casts, heme granular casts, hematuria or microhematuria (greater than 50 red blood cells per high power field in the absence of recent catheterization) on urinalysis (urine sediment examination is required to exclude presence of heme granular casts and other clinically significant casts). 17.Is known to be pregnant or breastfeeding. All females of child-bearing age and potential must have a negative pregnancy test. 18.Has severe cardiovascular disease, including, but not limited to, unstable angina, pulmonary edema, congestive heart failure requiring increasing doses of drug therapy, or persisting symptomatic peripheral vascular disease, myocardial infarction or stable chronic angina within the past 12 months, or any other cardiovascular disease judged by the investigator to be severe. 19.Has current or had recent (within 4 weeks) RRT or anticipation of RRT within 3 days of randomization. 20.Has participated in other clinical research involving investigational medicinal products within 30 days of randomization. 21.Has had TIPS placement within 30 days of randomization. 22.Has a known allergy or sensitivity to terlipressin or another component of the trial intervention. 23.Other potential participants who are judged by the principal investigator or sub investigator to be inappropriate for participation in the trial. 24.Has not experienced any adequate volume expansion (ie, pla
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the efficacy of terlipressin in the treatment of HRS in Japanese participants. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To assess the response to treatment with terlipressin in Japanese participants with HRS. - To assess the need for RRT in Japanese participants with HRS that are treated with terlipressin. - To assess the extent of improvement in renal function in Japanese participants treated with terlipressin for HRS. - To assess the rates of readmission in Japanese participants treated with terlipressin for HRS. | — |
Contacts
Public ContactTomohiro Taniguchi
Mallinckrodt Pharma K.K.
Outcome results
None listed