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, Lorenzo Rossaro, V. Araya, H. E. Vargas, K. R. Reddy, S. C. Pappas, P. Teuber, S. Escalante, K. Jamil

Research output: Contribution to journalArticle

18 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, Lorenzo; Araya, V.; Vargas, H. 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, Lorenzo ; Araya, V. ; Vargas, H. 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 Lorenzo Rossaro and V. Araya and Vargas, {H. 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, Lorenzo

AU - Araya, V.

AU - Vargas, H. 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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DO - 10.1111/apt.14052

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