title: 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.
abstract: 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.
  
  
  
  To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
authors.affiliation: Department of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: A J
authors.identifier: 0000-0001-8682-5748
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Department of Medicine, University of Arizona, Tucson, AZ, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Boyer
authors.affiliation: Department of Transplantation, California Pacific Medical Center, San Francisco, CA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Frederick
authors.affiliation: Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Wong
authors.affiliation: University of California Davis, Sacramento, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Rossaro
authors.affiliation: Department of Gastroenterology and Hepatology, Central Bucks Specialists, Ltd., Doylestown, PA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Araya
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Phoenix, AZ, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Vargas
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Reddy
authors.affiliation: Orphan Therapeutics, Lebanon, NJ, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Pappas
authors.affiliation: Orphan Therapeutics, Lebanon, NJ, USA.
authors.forename: P
authors.initials: P
authors.lastname: Teuber
authors.affiliation: Ikaria Therapeutics LLC/a Mallinckrodt Company, Hampton, NJ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Escalante
authors.affiliation: Ikaria Therapeutics LLC/a Mallinckrodt Company, Hampton, NJ, USA.
authors.forename: K
authors.initials: K
authors.lastname: Jamil
mesh_terms: D000328:Adult; D000418:Albumins / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D005260:Female; D006530:Hepatorenal Syndrome / Q000188:drug therapy*; D006801:Humans; D008236:Lypressin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D000077585:Terlipressin; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D000418:Albumins; D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin