CLINICAL RESPONSES TO TERLIPRESSIN IN THE SUBGROUP OF PATIENTS WITH HEPATORENAL SYNDROME FURTHER COMPOUNDED BY ALCOHOLIC HEPATITIS: ANALYSIS OF THE CONFIRM PHASE III STUDY

Background: Hepatorenal syndrome (HRS) with rapidly deteriorating kidney function can be effectively reversed when treated with terlipressin, the US FDA-approved vasopressin analogue. The Phase III placebo-controlled CONFIRM study demonstrated that verified HRS reversal was achieved in significantly more patients in the terlipressin group versus placebo (29.1% vs 15.8%; P=.012). However, clinical outcomes in patients with HRS may be influenced by the presence of alcoholic hepatitis (AH), which further confounds treatment options and harbors a poor prognosis. This subgroup analysis of the CONFIRM study assessed the efficacy of terlipressin in patients with HRS and AH.

Methods: The CONFIRM study enrolled adult patients with cirrhosis, ascites, and HRS with rapidly progressing kidney failure, defined per protocol as a doubling of serum creatinine to ≥2.25 mg/dL within 14 days (d) of randomization. Patients were randomly assigned 2:1 to terlipressin (1 mg by intravenous bolus every 6 hours) or placebo; concomitant albumin was recommended (1 g/kg on Day 1 up to 100 g then 20–40 g/d as clinically indicated). Diagnosis of baseline AH was via investigator assessment. Data was retrospectively analyzed in patients with AH for verified HRS reversal (defined as the percentage of patients with 2 serum creatinine values of ≤1.5 mg/dL ≥2 hours apart, while on treatment up to 72 hours after the last dose of study drug), admission to the intensive care unit (ICU), length of ICU stay, transplant-free survival at Day 90, and incidence of renal replacement therapy (RRT) by Day 30.

Results: In CONFIRM (N=300), 41% (81/199) of patients in the terlipressin group and 39% (39/101) of patients in the placebo group had AH at baseline. In the subgroup of patients with AH (n=120), the median Maddrey discriminant function score was similar across treatment groups (terlipressin, 96.9; placebo, 97.9; P=.681). Verified HRS reversal was achieved in 30.9% (25/81) of patients in the terlipressin group versus 7.7% (3/39) in the placebo group (P=.005) (Figure 1). Median transplant-free survival was 28 d for the terlipressin group versus 15 d for placebo (P=0.207) (Figure 2). Admission to the ICU was similar for patients in the terlipressin and placebo groups (17.3% [14/81] and 17.9% [7/39]); whereas mean length of stay in the ICU was shorter for terlipressin (6.9 d) versus the placebo group (12.4 d). There was a numerical decrease in RRT by Day 30 in the terlipressin versus placebo group (21.0% [17/81] vs 25.6% [10/39]).

Conclusions: In this cohort of patients with HRS and AH from CONFIRM, significantly more patients achieved verified HRS reversal with terlipressin than placebo. Additionally, in the terlipressin group numerical improvements in clinical outcomes included shorter duration of ICU stay, longer transplant-free survival, and lower incidence of RRT compared to placebo.