A Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 With Terlipressin

Inclusion Criteria

• Written informed consent by subject or legally authorized representative
• At least 18 years of age
• Cirrhosis and ascites
• Rapidly progressive reduction in renal function characterized by:
• Serum creatinine (SCr) ≥ 2.5 mg/dL
• Doubling of SCr within 2 weeks (or for observations of shorter duration, SCr values over time meeting slope-based criteria for proportional increases likely to be representative of at least a doubling within 2 weeks
• No sustained improvement in renal function ( 7 mg/dL
• Shock Note: Hypotension (Mean Arterial Pressure 40 mm Hg in systolic blood pressure from baseline) with evidence of hypoperfusion abnormalities despite adequate fluid resuscitation.
• Sepsis or systemic inflammatory response syndrome (SIRS)

Note: SIRS: Presence of 2 or more of the following findings:

Temperature > 38°C or 90/min; respiratory rate of > 20/min or a PaCO2 of 12,000 cells/µL or 500 mg/day

• Hematuria or microhematuria (> 50 red blood cells per high power field)
• Clinically significant casts on urinalysis, including granular casts Note: Urine sediment examination is required to exclude presence of granular casts and other clinically significant casts [e.g., red blood cell (RBC) casts].
• Evidence of intrinsic or parenchymal renal disease (including acute tubular necrosis)
• Obstructive uropathy or other renal pathology on ultrasound or other medical imaging
• Current or recent treatment (within 4 weeks) with nephrotoxic drugs, e.g., aminoglycosides, nonsteroidal anti-inflammatory drugs (NSAID) Note: Up to 3 doses of an NSAID within the prior month (prescription or over the counter) is acceptable Note: Use of short-term (< 2 weeks) oral neomycin for acute encephalopathy is acceptable.
• Current or recent (within 4 weeks) renal replacement therapy
• Superimposed acute liver failure/injury due to factors other than alcoholic hepatitis, including acute viral hepatitis, drugs, medications (e.g., acetaminophen), or other toxins (e.g., mushroom [Amanita] poisoning)
• Current or recent treatment (within 48 hours) with octreotide, midodrine, vasopressin, dopamine or other vasopressors
• Severe cardiovascular disease as judged by investigator
• Estimated life expectancy of less than 3 days
• Confirmed pregnancy
• Known allergy or sensitivity to terlipressin or another component of the study treatment
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization