Back to Journals » Open Access Journal of Clinical Trials » Volume 4

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

Authors Boyer, Medicis, Pappas, Potenziano, Jamil K

Received 16 March 2012

Accepted for publication 9 May 2012

Published 16 July 2012 Volume 2012:4 Pages 39—49


Review by Single-blind

Peer reviewer comments 2

Thomas D Boyer,1 Joseph J Medicis,2 Stephen Chris Pappas,3 Jim Potenziano,2 Khuramm Jamil2

1Department of Medicine, University of Arizona College of Medicine, Tucson, AZ, USA; 2Research and Development, Ikaria, Hampton, NJ, USA; 3Orphan Therapeutics, Lebanon, NJ, USA

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.

Keywords: terlipressin, Lucassin, hepatorenal syndrome, REVERSE, renal dysfunction, critical care

Corrigendum for this paper has been published

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 


Other article by this author:


Boyer TD, Medicis JJ, Pappas SC, Potenziano J, Jamil K

Open Access Journal of Clinical Trials 2012, 4:59-60

Published Date: 13 August 2012

Readers of this article also read:

Perioperative management of hemophilia patients receiving total hip and knee arthroplasty: a complication report of two cases

Tateiwa T, Takahashi Y, Ishida T, Kubo K, Masaoka T, Shishido T, Sano K, Yamamoto K

Therapeutics and Clinical Risk Management 2015, 11:1383-1389

Published Date: 15 September 2015

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Illicit methylphenidate use among Iranian medical students: prevalence and knowledge

Afshin Habibzadeh Mahasti Alizadeh Ayoub Malek, et al

Drug Design, Development and Therapy 2011, 5:71-76

Published Date: 3 February 2011

The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Rivka Yatuv, Micah Robinson, Inbal Dayan-Tarshish, et al

International Journal of Nanomedicine 2010, 5:581-591

Published Date: 6 August 2010

Induced pluripotent stem cells: advances to applications

Timothy J Nelson, Almudena Martinez-Fernandez, Satsuki Yamada, et al

Stem Cells and Cloning: Advances and Applications 2010, 3:29-37

Published Date: 22 December 2009