Study of Terlipressin Versus Placebo to Treat Hepatorenal Syndrome Type 1

Hepatorenal Syndrome Clinical Trial

Official title:

A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III Study of Intravenous Terlipressin in Patients With Hepatorenal Syndrome Type 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00089570
• Other study ID #: OT-0401
• Status: Completed
• Phase: Phase 3
• First received: August 6, 2004
• Last updated: October 25, 2017
• Start date: June 2004
• Est. completion date: September 2006

Study information

• Verified date: October 2017
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: September 2006
• Est. primary completion date: March 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatorenal Syndrome
• Syndrome

Intervention

Drug:
• terlipressin

• Placebo

Locations

Country	Name	City	State
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Lahey Clinic	Burlington	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center of Dallas	Dallas	Texas
United States	University of Colorado Hospital & Health Sciences Center	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	St. Luke's Episcopal Hospital, St. Luke's Texas Liver Institute	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	UCLA School of Medicine	Los Angeles	California
United States	Methodist University Hospital	Memphis	Tennessee
United States	Fairview-University Medical Center	Minneapolis	Minnesota
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Center for Liver Disease & Transplantation Clinic	New York	New York
United States	Mount Sinai Medical Center/Mount Sinai Hospital	New York	New York
United States	Weill Cornell Medical Center	New York	New York
United States	University of Medicine & Dentistry of New Jersey - NJMS	Newark	New Jersey
United States	983285 Nebraska Medical Center	Omaha	Nebraska
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Oregon Health Sciences University	Portland	Oregon
United States	VCU Medical Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UCSD Medical Center Hillcrest	San Diego	California
United States	VA Medical Center	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	University of Arizona College of Medicine	Tucson	Arizona
United States	Georgetown University Hospital	Washington, D.C.	District of Columbia
United States	VA CT Health Care System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt

Country where clinical trial is conducted

United States, 

References & Publications (10)

Arroyo V, Guevara M, Ginès P. Hepatorenal syndrome in cirrhosis: pathogenesis and treatment. Gastroenterology. 2002 May;122(6):1658-76. Review. — View Citation

Colle I, Durand F, Pessione F, Rassiat E, Bernuau J, Barrière 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. — View 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. — View 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. — View 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. — View Citation

Moreau R, Durand F, Poynard T, Duhamel C, Cervoni JP, Ichaï 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. — View 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. — View 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. — View Citation

Suzuki H, Stanley AJ. Current management and novel therapeutic strategies for refractory ascites and hepatorenal syndrome. QJM. 2001 Jun;94(6):293-300. Review. — View Citation

Uriz J, Ginès P, Cárdenas A, Sort P, Jiménez W, Salmerón JM, Bataller R, Mas A, Navasa M, Arroyo V, Rodés J. Terlipressin plus albumin infusion: an effective and safe therapy of hepatorenal syndrome. J Hepatol. 2000 Jul;33(1):43-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Success		Day 14
Secondary	Renal function and survival		Renal funtion to Day 14 and Survival to Day 180