A randomized, placebo-controlled, double-blind study to confirm the reversal of hepatorenal syndrome type 1 with terlipressin: The reverse trial design

Thomas D Boyer, Joseph J. Medicis, Stephen Chris Pappas, Jim Potenziano, Khuramm Jamil

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Hepatorenal syndrome (HRS) is a rare disorder of marked renal dysfunction in patients with cirrhosis, ascites, and portal hypertension. Type 1 HRS is a rapidly progressive acute kidney injury that develops shortly after a precipitating event, followed by a deterioration of function of other organs (eg, heart, brain, liver, adrenal glands). Presently, no approved drug therapies exist for HRS type 1 in the USA, Canada, or Australia. Given the rarity of this condition and the existing unmet medical need for treatment, the US Food and Drug Administration granted orphan drug and fast-track designations for terlipressin. The objective of the REVERSE trial was to determine the efficacy and safety of intravenous terlipressin compared with placebo in the treatment of adults with HRS type 1 who were also receiving intravenous albumin. Methods: 180 subjects with HRS type 1 were enrolled at 65 investigational sites located in the USA and ten sites in Canada. Patients were randomized in a 1:1 ratio to treatment with either intravenous terlipressin administered every 6 hours or placebo for up to 14 days. The primary efficacy measure was confirmed HRS reversal, defined as the percentage of patients with two serum creatinine values of ≤1.5 mg/dL at least 48 hours apart, on treatment, and without intervening renal replacement therapy or liver transplantation. Other efficacy measures included change in renal function as reflected in serum creatinine levels, fractional excretion of sodium, recurrence of HRS type 1, transplant-free, dialysis-free, and overall survival. Discussion: Data from this pivotal study are intended to demonstrate whether terlipressin is effective in reversing HRS type 1, while providing the level of evidence necessary to define the risk-benefit profile of terlipressin.

Original languageEnglish (US)
Pages (from-to)39-49
Number of pages11
JournalOpen Access Journal of Clinical Trials
Volume4
DOIs
StatePublished - May 24 2012

Fingerprint

Hepatorenal Syndrome
Double-Blind Method
Placebos
Canada
Creatinine
Orphan Drug Production
Kidney
Renal Replacement Therapy
terlipressin
Portal Hypertension
United States Food and Drug Administration
Therapeutics
Adrenal Glands
Serum
Acute Kidney Injury
Ascites
Liver Transplantation
Dialysis
Albumins
Fibrosis

Keywords

  • Critical care
  • Hepatorenal syndrome
  • Lucassin
  • Renal dysfunction
  • Reverse
  • Terlipressin

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
  • Pharmacology (medical)

Cite this

A randomized, placebo-controlled, double-blind study to confirm the reversal of hepatorenal syndrome type 1 with terlipressin : The reverse trial design. / Boyer, Thomas D; Medicis, Joseph J.; Pappas, Stephen Chris; Potenziano, Jim; Jamil, Khuramm.

In: Open Access Journal of Clinical Trials, Vol. 4, 24.05.2012, p. 39-49.

Research output: Contribution to journalArticle

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