TY - JOUR
T1 - A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome
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
AU - Teuber, Peter
N1 - Funding Information:
The study was supported in part by a grant from the Food and Drug Administration (FDA) (Office of Orphan Products Grant 1R01FD003024-01) and in part by Orphan Therapeutics. Orphan Therapeutics worked with the OT-0401 Executive and Steering Committees (membership listed in the Appendix ) in the design and conduct of the study and in the interpretation of the data and writing of the report. The FDA Office of Orphan Products reviewed the study protocol during the grant application process and monitored progress of the study; comments and guidance were provided to the OT-0401 Executive Committee.
PY - 2008/5
Y1 - 2008/5
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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U2 - 10.1053/j.gastro.2008.02.014
DO - 10.1053/j.gastro.2008.02.014
M3 - Article
C2 - 18471513
AN - SCOPUS:42949104076
SN - 0016-5085
VL - 134
SP - 1360
EP - 1368
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -