A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome

Arun J. Sanyal, Thomas Boyer, Guadalupe Garcia-Tsao, Frederick Regenstein, Lorenzo Rossaro, Beate Appenrodt, Andres Blei, Veit Gülberg, Samuel H. Sigal, Peter Teuber

Research output: Contribution to journalArticle

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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 anbxeffective treatment to improve renal function in HRS type 1.

Original languageEnglish (US)
Pages (from-to)1360-1368
Number of pages9
JournalGastroenterology
Volume134
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

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Hepatorenal Syndrome
Placebos
Creatinine
Serum
Dialysis
Transplantation
Therapeutics
terlipressin
Controlled Clinical Trials
Vasoconstrictor Agents
Renal Insufficiency
Liver Diseases
Albumins
Fibrosis
Myocardial Infarction
Kidney
Safety
Recurrence

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sanyal, A. J., Boyer, T., Garcia-Tsao, G., Regenstein, F., Rossaro, L., Appenrodt, B., ... Teuber, P. (2008). A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome. Gastroenterology, 134(5), 1360-1368. https://doi.org/10.1053/j.gastro.2008.02.014

A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome. / Sanyal, Arun J.; Boyer, Thomas; Garcia-Tsao, Guadalupe; Regenstein, Frederick; Rossaro, Lorenzo; Appenrodt, Beate; Blei, Andres; Gülberg, Veit; Sigal, Samuel H.; Teuber, Peter.

In: Gastroenterology, Vol. 134, No. 5, 05.2008, p. 1360-1368.

Research output: Contribution to journalArticle

Sanyal, AJ, Boyer, T, Garcia-Tsao, G, Regenstein, F, Rossaro, L, Appenrodt, B, Blei, A, Gülberg, V, Sigal, SH & Teuber, P 2008, 'A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome', Gastroenterology, vol. 134, no. 5, pp. 1360-1368. https://doi.org/10.1053/j.gastro.2008.02.014
Sanyal, Arun J. ; Boyer, Thomas ; Garcia-Tsao, Guadalupe ; Regenstein, Frederick ; Rossaro, Lorenzo ; Appenrodt, Beate ; Blei, Andres ; Gülberg, Veit ; Sigal, Samuel H. ; Teuber, Peter. / A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome. In: Gastroenterology. 2008 ; Vol. 134, No. 5. pp. 1360-1368.
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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 anbxeffective treatment to improve renal function in HRS type 1.",
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AU - Sanyal, Arun J.

AU - Boyer, Thomas

AU - Garcia-Tsao, Guadalupe

AU - Regenstein, Frederick

AU - Rossaro, Lorenzo

AU - Appenrodt, Beate

AU - Blei, Andres

AU - Gülberg, Veit

AU - Sigal, Samuel H.

AU - Teuber, Peter

PY - 2008/5

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N2 - 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 anbxeffective treatment to improve renal function in HRS type 1.

AB - 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 anbxeffective treatment to improve renal function in HRS type 1.

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