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

Authors

A. J. Sanyal, Virginia Commonwealth UniversityFollow
T. D. Boyer, University of Arizona
R. T. Frederick, California Pacific Medical Center
F. Wong, University of Toronto
L. Rossaro, University of California Davis
V. Araya, Central Bucks Specialists
H. E. Vargas, Mayo Clinic Arizona
K. R. Reddy, University of Pennsylvania
S. C. Pappas, Orphan Therapeutics
P. Teuber, Orphan Therapeutics
S. Escalante, Ikaria Therapeutics LLC
K. Jamil, Ikaria Therapeutics LLC

Document Type

Article

Original Publication Date

2017

Journal/Book/Conference Title

ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Volume

45

Issue

11

First Page

1390

Last Page

1402

DOI of Original Publication

10.1111/apt.14052

Comments

Originally published at http://doi.org/10.1111/apt.14052

Date of Submission

June 2017

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.

Rights

© 2017 The Authors. Alimentary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.

Is Part Of

VCU Internal Medicine Publications