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

Abstract

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.

• Authors: Arun J Sanyal, Thomas Boyer, Guadalupe Garcia-Tsao, Frederick Regenstein, Lorenzo Rossaro, Beate Appenrodt, Andres Blei, Veit Gülberg, Samuel Sigal, Peter Teuber, Terlipressin Study Group
• Journal: Gastroenterology (Gastroenterology) Vol. 134 Issue 5 Pg. 1360-8 (May 2008) ISSN: 1528-0012 [Electronic] United States
• PMID: 18471513 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Vasoconstrictor Agents
• Lypressin
• Terlipressin

Topics

• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Germany (epidemiology)
• Hepatorenal Syndrome (drug therapy, mortality, physiopathology)
• Humans
• Injections, Intravenous
• Kidney Function Tests
• Lypressin (administration & dosage, 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)