A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome

Gastroenterology. 2008 May;134(5):1360-8. doi: 10.1053/j.gastro.2008.02.014. Epub 2008 Feb 13.


Background & aims: Hepatorenal syndrome (HRS) type 1 is a progressive functional renal failure in subjects with advanced liver disease. The aim of this study was to evaluate the efficacy and safety of terlipressin, a systemic arterial vasoconstrictor, for cirrhosis type 1 HRS.

Methods: A prospective, randomized, double-blind, placebo-controlled clinical trial of terlipressin was performed. Subjects with type 1 HRS were randomized to terlipressin (1 mg intravenously every 6 hours) or placebo plus albumin in both groups. The dose was doubled on day 4 if the serum creatinine (SCr) level did not decrease by 30% of baseline. Treatment was continued to day 14 unless treatment success, death, dialysis, or transplantation occurred. Treatment success was defined by a decrease in SCr level to </=1.5 mg/dL for at least 48 hours by day 14 without dialysis, death, or relapse of HRS type 1.

Results: Fifty-six subjects were randomized to each arm. Treatment success with terlipressin was double that with placebo (25% vs 12.5%, P = .093). SCr level improved from baseline to day 14 on terlipressin (-0.7 mg/dL) as compared with placebo (0 mg/dL), P < .009. Terlipressin was superior to placebo for HRS reversal (34% vs 13%, P = .008), defined by decrease in SCr level </=1.5 mg/dL. Overall and transplantation-free survival was similar between study groups; HRS reversal significantly improved survival at day 180. One nonfatal myocardial infarction occurred with terlipressin, but the total adverse event rate was similar to placebo.

Conclusions: Terlipressin is an effective treatment to improve renal function in HRS type 1.

Trial registration: ClinicalTrials.gov NCT00089570.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Hepatorenal Syndrome / drug therapy*
  • Hepatorenal Syndrome / mortality
  • Hepatorenal Syndrome / physiopathology
  • Humans
  • Injections, Intravenous
  • Kidney Function Tests
  • Lypressin / administration & dosage
  • Lypressin / analogs & derivatives*
  • Male
  • Middle Aged
  • Prospective Studies
  • Russia / epidemiology
  • Severity of Illness Index
  • Shock, Septic
  • Survival Rate
  • Terlipressin
  • Treatment Outcome
  • United States / epidemiology
  • Vasoconstrictor Agents / administration & dosage*


  • Vasoconstrictor Agents
  • Lypressin
  • Terlipressin

Associated data

  • ClinicalTrials.gov/NCT00089570