The protocol subject to this grant application is Orphan Therapeutics Protocol OT-0401, entitled, """"""""A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase 3 Study of Intravenous Terlipressin in Patients with Hepatorenal Syndrome (HRS) Type 1."""""""" The primary objective of this trial is to demonstrate that intravenous terlipressin is safe and effective in the treatment of patients with HRS type 1 when compared to placebo. HRS is the development of renal dysfunction in patients with end-stage liver cirrhosis in the absence of any other cause of renal pathology. HRS type 1 is characterized by rapid deterioration of renal function, with marked increase in serum creatinine, azotemia, low urine output, dilutional hyponatremia and marked sodium retention, and a median survival time of less than 2 weeks. There is no available pharmacologic treatment for HRS type 1 in the U.S., therefore, there is a significant medical need for an effective and safe treatment. Terlipressin has shown activity in nine published clinical trials and retrospective studies (Hadengue 1998, Duhamel 2000, Uriz 2000, Mulkay 2001, Ortega 2002, Halimi 2002, Moreau 2002, Colle 2002, Solanki 2003). Protocol OT-0401 will enroll 120 patients of at least 18 years of age from both genders and all ethnicities and races. Patients' renal function, survival, and transplant status will be assessed to determine efficacy. Adverse events and laboratory assessments will be monitored and recorded to determine the safety of terlipressin in HRS type 1. The pharmacokinetics of terlipressin will also be assessed.
|Boyer, Thomas D; Sanyal, Arun J; Garcia-Tsao, Guadalupe et al. (2011) Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. J Hepatol 55:315-21|
|Sanyal, Arun J; Boyer, Thomas; Garcia-Tsao, Guadalupe et al. (2008) A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 134:1360-8|