Study of Terlipressin Versus Placebo to Treat Hepatorenal Syndrome Type 1

NCT00089570 | Completed Phase 3 DMC

• 1 other identifier: OT-0401
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 37

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.

Conditions

Hepatorenal Syndrome

Keywords

hepatorenal syndrome; terlipressin

Outcome Measures

Primary Outcomes (1)

• Treatment Success

  Day 14

Secondary Outcomes (1)

• Renal function and survival

  Renal funtion to Day 14 and Survival to Day 180

Study Arms (2)

Terlipressin

EXPERIMENTAL

Terlipressin

Drug: terlipressin

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

terlipressin DRUG

Terlipressin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mallinckrodt: lead

Study Sites (37)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

University of Arizona College of Medicine

Tucson, Arizona, 85724-5136, United States

Location

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UCSD Medical Center Hillcrest

San Diego, California, 92103-9707, United States

Location

VA Medical Center

San Diego, California, 92161, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California, San Francisco

San Francisco, California, 94143-0538, United States

Location

University of Colorado Hospital & Health Sciences Center

Denver, Colorado, 80262, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520-8019, United States

Location

VA CT Health Care System

West Haven, Connecticut, 06516, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Fairview-University Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

983285 Nebraska Medical Center

Omaha, Nebraska, 68198-3285, United States

Location

University of Medicine & Dentistry of New Jersey - NJMS

Newark, New Jersey, 07101-1709, United States

Location

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

Mount Sinai Medical Center/Mount Sinai Hospital

New York, New York, 10029, United States

Location

Center for Liver Disease & Transplantation Clinic

New York, New York, 10032, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-7080, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239-3098, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38103, United States

Location

University of Texas Southwestern Medical Center of Dallas

Dallas, Texas, 75390-9151, United States

Location

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

Houston, Texas, 77030, United States

Location

VCU Medical Center

Richmond, Virginia, 23298, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195-6174, United States

Location

Related Publications (16)

• 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.

  PMID: 12016430 BACKGROUND

• 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.

  PMID: 12164964 BACKGROUND

• 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.

  PMID: 11051385 BACKGROUND

• 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.

  PMID: 9824265 BACKGROUND

• 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.

  PMID: 11981339 BACKGROUND

• 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.

  PMID: 11910344 BACKGROUND

• 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.

  PMID: 11322061 BACKGROUND

• 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.

  PMID: 12542598 BACKGROUND

• 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.

  PMID: 11391027 BACKGROUND

• 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.

  PMID: 10905585 BACKGROUND

• 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 Dec;62(11-12):1192-1201. doi: 10.1111/apt.70297. Epub 2025 Jul 24.

  PMID: 40704461 DERIVED

• 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.

  PMID: 37302573 DERIVED

• 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.

  PMID: 37143199 DERIVED

• 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.

  PMID: 36633470 DERIVED

• 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.

  PMID: 28370090 DERIVED

• 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.

  PMID: 18471513 DERIVED

MeSH Terms

Conditions

Hepatorenal Syndrome

Interventions

Terlipressin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Arun J. Sanyal, M.D.

  Medical College of Virginia, Virginia Commonwealth University Medical Center

  STUDY CHAIR

• Thomas D. Boyer, M.D.

  University of Arizona Health Sciences Center

  STUDY DIRECTOR

• Peter Teuber, Ph.D.

  Orphan Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2004
• First Posted: August 9, 2004
• Study Start: June 1, 2004
• Primary Completion: March 1, 2006
• Study Completion: September 1, 2006
• Last Updated: October 27, 2017

Record last verified: 2017-10

Locations

US (37)