A Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 with Terlipressin Treatment

Overview

About this study

The purpose of this study is designed to evaluate the effectiveness and safety of intravenous Lucassin® (terlipressin) versus a placebo for the treatment of type 1 hepatorenal syndrome in patients receiving standard of care albumin therapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  • Written informed consent by subject or legally authorized representative
  • At least age 18 years
  • Cirrhosis and ascites
  • Rapidly progressive reduction in renal function characterized by
    • 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 (< 20% decrease in SCr and SCr ≥ 2.25 mg/dL) 48 hours after both diuretic withdrawal and the beginning of plasma volume expansion with albumin
    • Albumin doses recommended by the IAC are 1 g/kg on the first day (Maximum 100 g) and 20 - 40 g/day thereafter as clinically indicated
    • It is recommended (if clinically appropriate) that the albumin dose is kept constant during the study drug administration period
    • The qualifying SCr value is the SCr value at least 48 hrs after both diuretic withdrawal (if applicable) and the beginning of albumin fluid challenge
    • The qualifying SCr value must be ≥ 2.25 mg/dL and at least 80% of the diagnostic (pre-fluid challenge) SCr value

Exclusion Criteria

  • Serum Creatinine > 7 mg/dL
  • Shock hypotension mean arterial pressure < 70 mm Hg, or a decrease > 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) 
    • Presence of 2 or more of the following findings
      • Temperature > 38°C or < 36°C
      • Heart rate > 90/min
      • Respiratory rate of > 20/min
      • PaCO2 of < 32 mm Hg
      • White blood cell count of > 12,000 cells/µL or < 4,000/ µL
    • A septic documented infection and systemic inflammatory response syndrome
    • < 2 days anti-infective therapy for documented or suspected infection
  • Proteinuria > 500 mg/day
  • Hematuria or microhematuria (> 50 red blood cells per high power field)
  • Clinically significant casts on urinalysis, including granular casts 
    • 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)
    • Up to 3 doses of an NSAID within the prior month (prescription or over the counter) is acceptable 
    • 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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Hugo Vargas, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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Additional contact information

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