Retreatment Following Initial Treatment With Terlipressin Improved Clinical Outcomes Among Patients With Hepatorenal Syndrome-Acute Kidney Injury: A Pooled Post Hoc Analysis

Document Type

Conference Proceeding

Publication Date

10-1-2024

Publication Title

Am J Gastroenterol

Keywords

placebo, terlipressin, acute kidney failure, clinical outcome, conference abstract, controlled study, creatinine blood level, diagnosis, double blind procedure, drug therapy, female, hepatorenal syndrome, human, intention to treat analysis, major clinical study, male, phase 3 clinical trial, post hoc analysis, randomized controlled trial, recurrent disease, renal replacement therapy, retreatment, special situation for pharmacovigilance, therapy

Abstract

Introduction: Terlipressin is used to treat hepatorenal syndrome-acute kidney injury (HRS-AKI), a potentially lethal form of AKI. In 3 Phase III clinical studies of terlipressin treatment of patients with HRSAKI, retreatment with the same blinded study drug was allowed for patients who initially responded to treatment with a ≥30% reduction in serum creatinine (SCr), but then met the HRS diagnosis criteria again (≤90 days from the first dose of study drug). This study assessed retreatment with terlipressin and its associated clinical outcomes using pooled data from the 3 Phase III clinical studies. Methods: The intent-to-treat (ITT) population of 3 Phase III studies (ie, OT-0401, REVERSE, and CONFIRM), in which patients with HRS-AKI were treated with terlipressin at 1-2 mg every 6 hours via intravenous bolus or matched placebo, were pooled for the analysis. Retreatment was allowed if patients responded initially with a ≥30% reduction in SCr but then subsequently developed a recurrence of HRSAKI. HRS reversal was defined as ≥1 SCr value of ≤1.5 mg/dL on treatment (≤24 h after the last dose of study drug), for both the initial treatment and subsequent retreatment period. Assessments also included: durable HRS reversal, defined as HRS reversal without renal replacement therapy up to Day 30; and the proportion of patients alive at Day 90 (from start of initial treatment). Results: There was a significant improvement in HRS reversal and durable HRS reversal with initial terlipressin treatment versus placebo (HRS reversal: 33.2% [117/352] vs 16.4% [42/256], P< .01001; durable HRS reversal, 30.1% [106/352] vs 15.2% [39/256], P< .01001). Moreover, HRS reversal was durable among most patients with initial reversal (terlipressin, 90.6% [106/117]; placebo, 92.9% [39/42]). Ten patients eligible for retreatment with terlipressin were retreated, with a median time to retreatment of 21 days (range: 12-75 days). Among those retreated with terlipressin, 60% (6/10) achieved HRS reversal. Most patients (70.1% [82/117]) with initial HRS reversal in response to terlipressin treatment were alive at Day 90. Similarly, most patients (90% [9/10]) who initially responded but later required retreatment with terlipressin were also alive at Day 90. Conclusion: Terlipressin retreatment significantly improved HRS reversal, which was durable. Among patients eligible for retreatment with terlipressin due to recurrent HRS-AKI, 6/10 achieved HRS reversal and 9/10 were alive at Day 90. .

Volume

119

Issue

10

First Page

S1459

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