Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome
RCT (n=300 with cirrhosis) found terlipressin more effective than placebo in improving renal function, with verified reversal of hepatorenal syndrome (primary endpoint) reported in 32% and 17%, respectively (p=0.006), but was linked to serious ADRs including respiratory failure.
Source:
New England Journal of Medicine
SPS commentary:
This is one of two eagerly awaited multicentre, RCTs evaluating the management of decompensated cirrhosis in hospitalised.
In the Albumin to Prevent Infection in Chronic Liver Failure (ATTIRE) trial, (n=777), use of albumin infusions to increase albumin level to target of ≥30g/L was not more beneficial than the current standard care in UK (primary end-point of new infection, kidney dysfunction, or death between days 3 and 15 occurred in 29.7 vs. 30.2%, respectively).
According to an editorial, the performance of RCTs involving hospitalised patients with advanced cirrhosis is challenging. To facilitate the interpretation and comparability of results, future RCTs should define outcomes based on a set time from randomisation and assess all patients at this defined time point rather than discontinuing the assessment of the primary end point at the time of hospital discharge, as was the case in the design of both the ATTIRE and CONFIRM trials. It adds nevertheless, that these important trials showed, on the one hand, a lack of benefit of daily albumin infusions in hospitalised patients with decompensated cirrhosis and, on the other hand, a benefit of terlipressin in reversing hepatorenal syndrome. It notes however, that caution is required with both therapies regarding potentially lethal cardiopulmonary complications. It recommends that future investigations of terlipressin should refine the patient population that may benefit and evaluate the effectiveness of its continuous (rather than bolus) administration. In addition, validation of non-invasive methods to assess blood volume will be important in the management of decompensated cirrhosis in patients who are receiving albumin (per standard of care), particularly when this therapy is combined with terlipressin.