Study of Terlipressin Versus Placebo to Treat Hepatorenal Syndrome Type 1

NCT ID: NCT00089570

Last Updated: 2017-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-06-30

Study Completion Date

2006-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Hepatorenal Syndrome

Keywords

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hepatorenal syndrome terlipressin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Terlipressin

Terlipressin

Group Type EXPERIMENTAL

terlipressin

Intervention Type DRUG

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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terlipressin

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mallinckrodt

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arun J. Sanyal, M.D.

Role: STUDY_CHAIR

Medical College of Virginia, Virginia Commonwealth University Medical Center

Thomas D. Boyer, M.D.

Role: STUDY_DIRECTOR

University of Arizona Health Sciences Center

Peter Teuber, Ph.D.

Role: STUDY_DIRECTOR

Orphan Therapeutics

Locations

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Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

University of Arizona College of Medicine

Tucson, Arizona, United States

Site Status

UCLA School of Medicine

Los Angeles, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

UCSD Medical Center Hillcrest

San Diego, California, United States

Site Status

VA Medical Center

San Diego, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of Colorado Hospital & Health Sciences Center

Denver, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

VA CT Health Care System

West Haven, Connecticut, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Lahey Clinic

Burlington, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Fairview-University Medical Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

983285 Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

University of Medicine & Dentistry of New Jersey - NJMS

Newark, New Jersey, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

Mount Sinai Medical Center/Mount Sinai Hospital

New York, New York, United States

Site Status

Center for Liver Disease & Transplantation Clinic

New York, New York, United States

Site Status

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Oregon Health Sciences University

Portland, Oregon, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Methodist University Hospital

Memphis, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center of Dallas

Dallas, Texas, United States

Site Status

St. Luke's Episcopal Hospital, St. Luke's Texas Liver Institute

Houston, Texas, United States

Site Status

VCU Medical Center

Richmond, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 12016430 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12164964 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11051385 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9824265 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11981339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11910344 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11322061 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12542598 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11391027 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10905585 (View on PubMed)

Bajaj JS, Kwo P, Pappas SC, O'Leary JG, Jamil K, Cardoza S, Wong F. Bradycardia and Other Arrhythmias in Patients With Hepatorenal Syndrome-Acute Kidney Injury Following Terlipressin Treatment: A Pooled Analysis of Three North American Phase III Clinical Studies. Aliment Pharmacol Ther. 2025 Jul 24. doi: 10.1111/apt.70297. Online ahead of print.

Reference Type DERIVED
PMID: 40704461 (View on PubMed)

Mujtaba MA, Gamilla-Crudo AK, Merwat SN, Hussain SA, Kueht M, Karim A, Khattak MW, Rooney PJ, Jamil K. Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older. Ann Hepatol. 2023 Sep-Oct;28(5):101126. doi: 10.1016/j.aohep.2023.101126. Epub 2023 Jun 10.

Reference Type DERIVED
PMID: 37302573 (View on PubMed)

Velez JCQ, Wong F, Reddy KR, Sanyal AJ, Vargas HE, Curry MP, Gonzalez SA, Pappas SC, Jamil K. The Effect of Terlipressin on Renal Replacement Therapy in Patients with Hepatorenal Syndrome. Kidney360. 2023 Aug 1;4(8):1030-1038. doi: 10.34067/KID.0000000000000132. Epub 2023 May 5.

Reference Type DERIVED
PMID: 37143199 (View on PubMed)

Curry MP, Vargas HE, Befeler AS, Pyrsopoulos NT, Patwardhan VR, Jamil K. Early treatment with terlipressin in patients with hepatorenal syndrome yields improved clinical outcomes in North American studies. Hepatol Commun. 2023 Jan 3;7(1):e1307. doi: 10.1097/01.HC9.0000897228.91307.0c. eCollection 2023 Jan 1.

Reference Type DERIVED
PMID: 36633470 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28370090 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18471513 (View on PubMed)

Other Identifiers

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OT-0401

Identifier Type: -

Identifier Source: org_study_id