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

SummaryBackgroundThe 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.AimTo compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS‐1.MethodsPooled 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.ResultsThe 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.ConclusionsTerlipressin 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).

Clinical trial watch: Reports from the AASLD Liver Meeting®, Boston, November 2014

“…The same authors presented [22] the pooled data from this study and a previous one with similar design [23], showing a significant improvement in the rate of confirmed HRS reversal. Survival was significantly higher and need for renal replacement therapy lower in patients achieving reversal.…”

Hepatorenal syndrome in the era of acute kidney injury

“…However, a continued analysis of patients included in the REEVRSE trial as well as in a previous trial in North America (OT‐0401) demonstrated that treatment with terlipressin plus albumin in patients with HRS‐1 resulted in a significantly higher rate of HRS reversal compared to that of patients who received albumin alone, confirming that terlipressin treatment is associated with improved renal function …”

“…However, a continued analysis of patients included in the REEVRSE trial as well as in a previous trial in North America (OT-0401) demonstrated that treatment with terlipressin plus albumin in patients with HRS-1 resulted in a significantly higher rate of HRS reversal compared to that of patients who received albumin alone, confirming that terlipressin treatment is associated with improved renal function. 53 During treatment with terlipressin patients must receive concomitant treatment with IV albumin at a dose of 1 g/kg body weight the first day followed by 20-40 g/d. 41,54 As mentioned above, it is recommended to monitor central venous pressure during treatment.…”

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology

“…The diagnosis requires demonstration of a recent rise in SCr and exclusion of other causes of AKI such as hypovolaemia, drugs and parenchymal renal disease. There are data showing that early initiation of treatment with vasoconstrictor therapy coupled with albumin infusion might improve patient survival and renal outcomes …”