Clinical Trials

Inclusion Criteria:

• Written informed consent by subject or legally authorized representative.
• At least 18 years of age.
• 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.

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 (eg, persisting bacteremia, persisting ascitic fluid leucocytosis, fever, increasing leucocytosis with vasomotor instability).
• Less than 2 days anti-infective therapy for documented or suspected infection.
• Shock.
• Current or 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).
• Estimated life expectancy of less than 3 days.
• 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.
• 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.
  • Note: Urine sediment examination is required to exclude presence of heme granular casts and other clinically significant casts.
• Subjects known to be pregnant; all women of child-bearing age and potential must have a negative pregnancy test.
• 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.
• Current or recent (within 4 weeks) renal replacement therapy (RRT).
• 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 (eg, norepinephrine, epinephrine or vasopressin dopamine or other vasopressors ) of at least 3 consecutive days within the prior 14-day screening period. Patients receiving a vasopressor other than midodrine within 24 hours of qualifying SCr are excluded, ie, a 24-h washout is required prior to enrollment.
  • Note: Patients receiving midodrine and octreotide may be enrolled. Midodrine and octreotide treatment must be stopped prior to randomization.
• Known allergy or sensitivity to terlipressin or another component of the study treatment.