Author information

¹University of Texas Medical Branch, 301 University Blvd, Galveston, TX, USA. Electronic address: mamujtab@utmb.edu.

²University of Texas Medical Branch, 301 University Blvd, Galveston, TX, USA.

³Texas Health Presbyterian Hospital, 8200 Walnut Hill Ln, Dallas, TX, USA.

⁴University of Illinois College of Medicine, 1 Illini Dr, Peoria, IL, USA.

⁵Mallinckrodt Pharmaceuticals, 53 I-78 Frontage Rd, Hampton, NJ, USA.

Abstract

Introduction and objectives: Clinical data for older patients with advanced liver disease are limited. This post hoc analysis evaluated the efficacy and safety of terlipressin in patients aged ≥65 years with hepatorenal syndrome using data from 3 Phase III, randomized, placebo-controlled studies (OT-0401, REVERSE, CONFIRM).

Patients and methods: The pooled population of patients aged ≥65 years (terlipressin, n = 54; placebo, n = 36) was evaluated for hepatorenal syndrome reversal-defined as a serum creatinine level ≤1.5 mg/dL (≤132.6 μmol/L) while receiving terlipressin or placebo, without renal replacement therapy, liver transplantation, or death-and the incidence of renal replacement therapy (RRT). Safety analyses included an assessment of adverse events.

Results: Hepatorenal syndrome reversal was almost 2-times higher in terlipressin-treated patients compared with patients who received placebo (31.5% vs 16.7%; P = 0.143). Among surviving patients, the need for RRT was significantly reduced in the terlipressin group, with an almost 3-times lower incidence of RRT versus the placebo group (Day 90: 25.0% vs 70.6%; P = 0.005). Among 23 liver-transplant-listed patients, significantly fewer patients in the terlipressin versus placebo group needed RRT by Days 30 and 60 (P = 0.027 each). Fewer patients in the terlipressin group needed RRT post-transplant (P = 0.011). More terlipressin-treated patients who were listed for and received a liver transplant were alive and RRT-free by Day 90. No new safety signals were revealed in the older subpopulation compared with previously published data.

Conclusions: Terlipressin therapy may lead to clinical improvements in highly vulnerable patients aged ≥65 years with hepatorenal syndrome.

Clinical trial numbers: OT-0401, NCT00089570; REVERSE, NCT01143246; CONFIRM, NCT02770716.