Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies

A. J. Sanyal, T. D. Boyer, R. T. Frederick, F. Wong, L. Rossaro, V. Araya, Hugo E Vargas, K. R. Reddy, S. C. Pappas, P. Teuber, S. Escalante, K. Jamil

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods: Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results: The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions: Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).

Original languageEnglish (US)
JournalAlimentary Pharmacology and Therapeutics
DOIs
StateAccepted/In press - 2017

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Hepatorenal Syndrome
Albumins
Placebos
Creatinine
Kidney
Serum
Clinical Studies
terlipressin
Precipitating Factors
Renal Replacement Therapy
Survival
Vasoconstrictor Agents
Therapeutics
Vasopressins
Bilirubin
Arterial Pressure

ASJC Scopus subject areas

  • Pharmacology (medical)

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Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. / Sanyal, A. J.; Boyer, T. D.; Frederick, R. T.; Wong, F.; Rossaro, L.; Araya, V.; Vargas, Hugo E; Reddy, K. R.; Pappas, S. C.; Teuber, P.; Escalante, S.; Jamil, K.

In: Alimentary Pharmacology and Therapeutics, 2017.

Research output: Contribution to journalArticle

Sanyal, A. J. ; Boyer, T. D. ; Frederick, R. T. ; Wong, F. ; Rossaro, L. ; Araya, V. ; Vargas, Hugo E ; Reddy, K. R. ; Pappas, S. C. ; Teuber, P. ; Escalante, S. ; Jamil, K. / Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. In: Alimentary Pharmacology and Therapeutics. 2017.
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abstract = "Background: The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods: Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results: The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27{\%} vs. 14{\%}; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions: Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).",
author = "Sanyal, {A. J.} and Boyer, {T. D.} and Frederick, {R. T.} and F. Wong and L. Rossaro and V. Araya and Vargas, {Hugo E} and Reddy, {K. R.} and Pappas, {S. C.} and P. Teuber and S. Escalante and K. Jamil",
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T1 - Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies

AU - Sanyal, A. J.

AU - Boyer, T. D.

AU - Frederick, R. T.

AU - Wong, F.

AU - Rossaro, L.

AU - Araya, V.

AU - Vargas, Hugo E

AU - Reddy, K. R.

AU - Pappas, S. C.

AU - Teuber, P.

AU - Escalante, S.

AU - Jamil, K.

PY - 2017

Y1 - 2017

N2 - Background: The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods: Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results: The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions: Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).

AB - Background: The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods: Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results: The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions: Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).

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