Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1
Condition: Hepatorenal Syndrome
MeSH terms: Hepatorenal Syndrome; Syndrome
Intervention: Terlipressin; Placebo
Intervention description: Terlipressin solution for injection; Matching placebo solution for injection
Intervention MeSH terms: Terlipressin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Type 1

Summary:

      This study is to treat adult patients with hepatorenal syndrome (HRS) Type 1.

      Out of every three participants, two will receive terlipressin and one will receive placebo.

      Assignments will be made randomly.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent by participant or legally authorized representative

          -  Cirrhosis and ascites

          -  Rapidly progressive worsening in renal function to a serum creatinine (SCr) at least
             2.25 mg/dL and meeting a trajectory for SCr to double over 2 weeks

          -  No sustained improvement in renal function (less than 20% decrease in SCr and SCr at
             least 2.25 mg/dL) at least 48 hours after diuretic withdrawal and the beginning of
             plasma volume expansion with albumin

          -  Discontinues midodrine and octreotide before randomization if applicable

        Exclusion Criteria:

          -  Serum creatinine level greater than 7.0 mg/dL

          -  At least 1 event of large volume paracentesis (LVP) at least 4 L within 2 days of
             randomization

          -  Sepsis and/or uncontrolled bacterial infection

          -  Less than 2 days anti-infective therapy for documented or suspected infection

          -  Shock

          -  Being treatment with or exposure to nephrotoxic agents, nonsteroidal anti-inflammatory
             drugs, or significant radiographic contrast agents (within the last 4 weeks)

          -  Estimated life expectancy of less than 3 days

          -  Superimposed acute liver injury due to drugs, dietary supplements, herbal
             preparations, viral hepatitis, or toxins, with the exception of acute alcoholic
             hepatitis

          -  Proteinuria greater than 500 mg/day

          -  Evidence of obstructive uropathy or parenchymal renal disease on ultrasound or other
             imaging

          -  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

          -  Pregnancy; all women of child-bearing age and potential must have a negative pregnancy
             test

          -  Cardiovascular disease judged by the investigator to be severe

          -  Current or recent renal replacement therapy (RRT) within the past 4 weeks

          -  Participation in other clinical research involving investigational medicinal products
             within 30 days of randomization

          -  Transjugular intrahepatic portosystemic shunt (TIPS) within 30 days of randomization

          -  Use of vasopressors for at least 3 consecutive days within the 14-day screening period
             - patients receiving any vasopressor other than midodrine and octreotide within 24
             hours of qualifying SCr are also excluded, ie, a 24-hour washout is required prior to
             enrollment

          -  Known allergy or sensitivity to terlipressin or another component of the study
             treatment