Clinical Data Analysis on Terlipressin Presented at The Liver Meeting®
Terlipressin is being investigated for the treatment of HRS-1, an acute, rare and life-threatening condition requiring hospitalization, with currently no approved therapy in the U.S. or
"Patients diagnosed with HRS-1 typically have a very poor prognosis, and there is a significant unmet need for an approved treatment," said
Data were analyzed for the predictive value of HRS-1 reversal (20% or 30% improvement in SCr) for survival and the use of Renal Replacement Therapy (RRT). Positive predictive value (PPV), negative predictive value (NPV), accuracy, sensitivity, and specificity were determined using standard definitions. Receiver operator curves (ROCs) were generated for overall survival by improvement in SCr from baseline to the end of treatment and HRS-1 reversal by improvement in SCr from baseline to end of treatment. Youden's index as an estimate of optimal cutoff for the ROCs was derived using the standard formula (Youden index = sensitivity + specificity – 1).9
Improvement in SCr had similar PPV, NPV, sensitivity, and specificity as HRS-1 reversal in predicting survival; HRS-1 reversal and improvement in SCr were similarly accurate in predicting the use of RRT. The number of patients achieving at least a 20% improvement in SCr was twice that of those achieving HRS-1 reversal in these two large studies. Small improvements in SCr of 15% were associated with increased survival; an improvement in SCr of 40% was the optimal cutoff for achieving HRS-1 reversal. More specific analysis results follow:
- 64 patients (21%) achieved HRS-1 reversal and 118 patients (38%) had at least a 20% fall in SCr.
- A 20% reduction in SCr gave predictive, sensitivity and specificity values that were similar to HRS-1 reversal for survival; 30% improvement in SCr did not increase accuracy.
- For RRT, results were similar; HRS-1 reversal was somewhat more accurate in predicting the use of RRT.
- HRS-1 reversal or improvement in SCr reduced the use of RRT from 50‒56% to 9‒12%.
- The number of patients achieving ≥20% improvement in SCr was twice that of those achieving HRS-1 reversal in these two large studies.
- The highest values for the Youden index for overall survival was 0.353, suggesting an optimal cutoff of 15% improvement in SCr from baseline to end of treatment. The highest value of the Youden index for HRS-1 reversal was 0.896, suggesting an optimal cutoff of 40% improvement in SCr from baseline to end of treatment.
This study is a post-hoc analysis of completed clinical trials.
About Hepatorenal Syndrome
HRS type 1 is characterized by a rapid, progressive renal impairment and has a very poor prognosis, with >80% mortality within three months. HRS is a rare syndrome of marked renal dysfunction in patients with cirrhosis, decompensated liver disease and portal hypertension. At present, there are no approved drug therapies for HRS type 1 in the U.S. or
Terlipressin is a synthetic vasopressin analogue in development for the treatment of HRS type 1 in the U.S. and
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1 Copyright & Trademark. The American Association for the Study of Liver Diseases (AASLD). Available at: http://www.aasld.org/copyright-trademark. Accessed November 15, 2016.
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6 Boyer TD, Sanyal AJ, Wong F, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterology. 2016;150:1579-1589.
7 Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360-1368.
8 A Study To Confirm Efficacy and Safety of Terlipressin in HRS Type 1. ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT02770716. Accessed November 15, 2016.
9 ROC Curves in NCSS. NCSS Statistical Software Web Site. Available at: https://www.ncss.com/software/ncss/roc-curves-ncss/. Accessed November 15, 2016.
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