Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1

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