Clinical trial NCT00089570: Study of Terlipressin Versus Placebo to Treat Hepatorenal Syndrome Type 1
Official title: A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III Study of Intravenous Terlipressin in Patients With Hepatorenal Syndrome Type 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatorenal Syndrome
Keywords: hepatorenal syndrome
terlipressin
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2004-08-09
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether terlipressin is safe and effective in the treatment of patients with hepatorenal syndrome (HRS) type 1 when compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Chronic, or acute liver disease
* Rapidly progressive reduction in renal function, e.g. doubling of serum creatinine to \>2.5 mg/dL in less than two weeks.
* No sustained improvement in renal function after diuretic withdrawal and plasma volume expansion
* Proteinuria \<500 mg per day
* No evidence of granular casts in urinalysis or ultrasonographic evidence of obstructive uropathy or parenchymal renal disease

Exclusion Criteria:

* Ongoing shock
* Uncontrolled bacterial infection
* Current significant fluid losses
* Current or recent treatment with nephrotoxic drugs (e.g. NSAIDs or aminoglycosides within 4 weeks)
* Acute liver disease due to factors known to be also directly nephrotoxic (e.g. acetaminophen overdose)
* Confirmed pregnancy
* Severe cardiovascular disease
* Evidence of intrinsic or parenchymal renal disease (e.g. acute tubular necrosis)
* Participation in other clinical studies within 30 days

Primary outcomes:
measure: Treatment Success
timeFrame: Day 14
Secondary outcomes:
measure: Renal function and survival
timeFrame: Renal funtion to Day 14 and Survival to Day 180
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Tucson
country: United States
facility: University of Arizona College of Medicine
state: Arizona
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center Hillcrest
state: California
city: San Diego
country: United States
facility: VA Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado Hospital & Health Sciences Center
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: West Haven
country: United States
facility: VA CT Health Care System
state: Connecticut
city: Washington, D.C.
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Fairview-University Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: 983285 Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: University of Medicine & Dentistry of New Jersey - NJMS
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center/Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Center for Liver Disease & Transplantation Clinic
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Methodist University Hospital
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center of Dallas
state: Texas
city: Houston
country: United States
facility: St. Luke's Episcopal Hospital, St. Luke's Texas Liver Institute
state: Texas
city: Richmond
country: United States
facility: VCU Medical Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Medical College of Virginia, Virginia Commonwealth University Medical Center
name: Arun J. Sanyal, M.D.
role: STUDY_CHAIR
affiliation: University of Arizona Health Sciences Center
name: Thomas D. Boyer, M.D.
role: STUDY_DIRECTOR
affiliation: Orphan Therapeutics
name: Peter Teuber, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Arroyo V, Guevara M, Gines P. Hepatorenal syndrome in cirrhosis: pathogenesis and treatment. Gastroenterology. 2002 May;122(6):1658-76. doi: 10.1053/gast.2002.33575. No abstract available.
citation: Colle I, Durand F, Pessione F, Rassiat E, Bernuau J, Barriere E, Lebrec D, Valla DC, Moreau R. Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with Terlipressin: a retrospective analysis. J Gastroenterol Hepatol. 2002 Aug;17(8):882-8. doi: 10.1046/j.1440-1746.2002.02816.x.
citation: Duhamel C, Mauillon J, Berkelmans I, Bourienne A, Tranvouez JL. Hepatorenal syndrome in cirrhotic patients: terlipressine is a safe and efficient treatment; propranolol and digitalic treatments: precipitating and preventing factors? Am J Gastroenterol. 2000 Oct;95(10):2984-5. doi: 10.1111/j.1572-0241.2000.03214.x. No abstract available.
citation: Hadengue A, Gadano A, Moreau R, Giostra E, Durand F, Valla D, Erlinger S, Lebrec D. Beneficial effects of the 2-day administration of terlipressin in patients with cirrhosis and hepatorenal syndrome. J Hepatol. 1998 Oct;29(4):565-70. doi: 10.1016/s0168-8278(98)80151-7.
citation: Halimi C, Bonnard P, Bernard B, Mathurin P, Mofredj A, di Martino V, Demontis R, Henry-Biabaud E, Fievet P, Opolon P, Poynard T, Cadranel JF. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol. 2002 Feb;14(2):153-8. doi: 10.1097/00042737-200202000-00009.
citation: Moreau R, Durand F, Poynard T, Duhamel C, Cervoni JP, Ichai P, Abergel A, Halimi C, Pauwels M, Bronowicki JP, Giostra E, Fleurot C, Gurnot D, Nouel O, Renard P, Rivoal M, Blanc P, Coumaros D, Ducloux S, Levy S, Pariente A, Perarnau JM, Roche J, Scribe-Outtas M, Valla D, Bernard B, Samuel D, Butel J, Hadengue A, Platek A, Lebrec D, Cadranel JF. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology. 2002 Apr;122(4):923-30. doi: 10.1053/gast.2002.32364.
citation: Mulkay JP, Louis H, Donckier V, Bourgeois N, Adler M, Deviere J, Le Moine O. Long-term terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study. Acta Gastroenterol Belg. 2001 Jan-Mar;64(1):15-9.
citation: Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol. 2003 Feb;18(2):152-6. doi: 10.1046/j.1440-1746.2003.02934.x.
citation: Suzuki H, Stanley AJ. Current management and novel therapeutic strategies for refractory ascites and hepatorenal syndrome. QJM. 2001 Jun;94(6):293-300. doi: 10.1093/qjmed/94.6.293.
citation: Uriz J, Gines P, Cardenas A, Sort P, Jimenez W, Salmeron JM, Bataller R, Mas A, Navasa M, Arroyo V, Rodes J. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol. 2000 Jul;33(1):43-8. doi: 10.1016/s0168-8278(00)80158-0.
citation: Sanyal AJ, Boyer TD, Frederick RT, Wong F, Rossaro L, Araya V, Vargas HE, Reddy KR, Pappas SC, Teuber P, Escalante S, Jamil K. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies. Aliment Pharmacol Ther. 2017 Jun;45(11):1390-1402. doi: 10.1111/apt.14052. Epub 2017 Mar 29.
citation: Sanyal AJ, Boyer T, Garcia-Tsao G, Regenstein F, Rossaro L, Appenrodt B, Blei A, Gulberg V, Sigal S, Teuber P; Terlipressin Study Group. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008 May;134(5):1360-8. doi: 10.1053/j.gastro.2008.02.014. Epub 2008 Feb 13.