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

Aliment Pharmacol Ther. 2017 Jun;45(11):1390-1402. doi: 10.1111/apt.14052. Epub 2017 Mar 29.


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. ( identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Albumins / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Drug Therapy, Combination
  • Female
  • Hepatorenal Syndrome / drug therapy*
  • Humans
  • Lypressin / analogs & derivatives*
  • Lypressin / therapeutic use
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Terlipressin
  • Treatment Outcome
  • Vasoconstrictor Agents / therapeutic use*


  • Albumins
  • Vasoconstrictor Agents
  • Lypressin
  • Terlipressin

Associated data