BOSTON – Treating patients with hepatorenal syndrome type 1 for up to 14 days using terlipressin plus albumin rather than albumin alone did not improve the chances of confirmed reversal of hepatorenal syndrome in a multicenter, randomized, double-blind, placebo-controlled trial in 196 patients.
Investigators confirmed reversal of hepatorenal syndrome type 1 (HRS-1) in 19 of 97 patients on terlipressin plus albumin (20%) and 13 of 99 patients on albumin plus placebo (13%), a difference between groups that was not statistically significant, Dr. Thomas D. Boyer reported at the annual meeting of the American Association for the Study of Liver Diseases.
Dr. Thomas Boyer
He and his associates defined confirmed reversal of HRS-1 as two serum creatinine values no higher than 1.5 mg/dL at least 48 hours apart while on treatment, without renal replacement therapy or liver transplant.
Secondary outcomes included reversal of HRS-1, defined as a decrease in serum creatinine to no higher than 1.5 mg/dL. This goal was reached by 23 patients on terlipressin plus albumin, and 15 patients on albumin alone achieved reversal of HRS-1 (24% vs. 15%, respectively), a difference that also was not statistically significant.
Among other secondary outcomes, though, terlipressin showed some potential advantages in subgroup analyses, said Dr. Boyer, professor of medicine and director of the Liver Research Institute at the University of Arizona, Tucson.
Significantly greater improvements in serum creatinine during treatment with terlipressin correlated with survival. Compared with baseline levels, serum creatinine decreased by 1.2 mg/dL in the terlipressin group and 0.6 mg/dL in the placebo group, a statistically significant difference between groups.
All 19 patients who achieve confirmed reversal of HRS-1 on terlipressin were alive without renal replacement therapy at 90-day follow-up, significantly more than the 6 of 13 patients with confirmed reversal of HRS-1 in the placebo group who remained alive at 90 days (46%).
Overall survival and transplant-free survival rates did not differ significantly between groups.
Serious adverse events occurred in 59 patients in the terlipressin group (61%) and 53 patients in the placebo group (54%), rates that did not differ significantly between groups. No new or unexpected adverse events were seen.
The REVERSE trial (Phase III, Multi-Center Randomized, Placebo-Controlled, Double-Blind Study to Confirm the Reversal of Hepatorenal Syndrome Type 1 with Lucassin [Terlipressin]) enrolled adults with cirrhosis, ascites, and HRS-1. The study defined HRS-1 as rapidly deteriorating renal function that didn’t improve within 48 hours of diuretic withdrawal and albumin-fluid challenge. Rapidly deteriorating renal function was defined as a serum creatinine level of at least 2.5 mg/dL and actual or projected doubling of serum creatinine within 2 weeks. Improvement in renal function was defined as less than a 20% decrease in serum creatinine and a serum creatinine level of at least 2.5 mg/dL.
Patients received IV infusions of 6 mg terlipressin or placebo every 6 hours, plus albumin.
Ikaria, which markets terlipressin (Lucassin), funded the study. Dr. Boyer is a consultant for Ikaria and he reported financial associations with AbbVie, Gilead, and Merck. His associates reported financial associations with Ikaria and multiple companies.
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