Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: A retrospective multicenter study

A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of Terlipressin for Type 1 Hepatorenal Syndrome

“…[30][31][32] The current phase III randomized clinical trial confirms the findings of previous uncontrolled and small controlled pilot studies that terlipressin, a systemic vasoconstrictor, improves renal function in HRS type 1. [17][18][19] In this study, patients who received terlipressin had significant improvements in renal function relative to controls, although the difference between the treated (25%) and control groups (12.5%) did not reach statistical significance when the primary end point of treatment success at day 14 was used. The end point routinely applied in the literature, HRS reversal (SCr level ≤1.5 mg/dL), [14][15][16][17][23][24][25] was, however, achieved in significantly more patients receiving terlipressin (33.9%) as compared with controls (12.5%).…”

“…[17][18][19] In this study, patients who received terlipressin had significant improvements in renal function relative to controls, although the difference between the treated (25%) and control groups (12.5%) did not reach statistical significance when the primary end point of treatment success at day 14 was used. The end point routinely applied in the literature, HRS reversal (SCr level ≤1.5 mg/dL), [14][15][16][17][23][24][25] was, however, achieved in significantly more patients receiving terlipressin (33.9%) as compared with controls (12.5%). The response to treatment was also durable, with a HRS type 1 relapse rate of 5.3% among responders to terlipressin vs 14.3% for those who responded to placebo.…”

“…The treatment success end point was developed by the study investigators as a more stringent version of the traditional end point of "HRS reversal," which is defined as a decrease in SCr level to ≤1.5 mg/dL during treatment without dialysis. [14][15][16][17][23][24][25] An analysis of HRS reversal was also planned to provide a comparison between the current study and data published in the literature.…”

“…The estimated rate of treatment success at day 14 for the terlipressin group was based on largely uncontrolled studies published in the literature, which reported HRS reversal in approximately 50%-60% of patients treated with terlipressin and albumin. [14][15][16][17][23][24][25] Considering the more rigorous definition of treatment success used in this study (ie, SCr level ≤1.5 mg/dL on 2 occasions at least 48 hours apart, without dialysis, death, or recurrence of HRS within the 14 day treatment period), it was projected that 35% and 5% of patients in the terlipressin plus albumin and placebo plus albumin groups, respectively, would achieve the primary end point.…”

“…A variety of vasoconstrictors including terlipressin, ornipressin, midodrine plus octreotide, and norepinephrine have been used in uncontrolled trials 9,10 ; of these, terlipressin, a 12-amino acid synthetic analogue of lysine-vasopressin, 11 is the most studied. [12][13][14][15][16][17] In 2 small, randomized, single-blind pilot studies with a brief period of follow-up, terlipressin plus albumin was shown to improve serum creatinine (SCr) more effectively as compared with placebo plus albumin. 18,19 In a meta-analysis of the latter and other uncontrolled trials, terlipressin was reported to reverse HRS type 1 in up to 50% of subjects.…”