Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1

NCT ID: NCT02770716

Last Updated: 2022-11-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-13

Study Completion Date

2019-07-24

Brief Summary

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This study is to treat adult patients with hepatorenal syndrome (HRS) Type 1.

Out of every three participants, two will receive terlipressin and one will receive placebo.

Assignments will be made randomly.

Detailed Description

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The primary objective of this trial is to confirm the efficacy and safety of intravenous terlipressin versus placebo in the treatment of adult subjects with hepatorenal syndrome (HRS) Type 1.

Conditions

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Hepatorenal Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Terlipressin

Participants receive terlipressin intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.

Group Type EXPERIMENTAL

Terlipressin

Intervention Type DRUG

Terlipressin solution for injection

Placebo

Participants receive matching placebo intravenously as a bolus injection, followed by a saline flush. Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching placebo solution for injection

Interventions

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Terlipressin

Terlipressin solution for injection

Intervention Type DRUG

Placebo

Matching placebo solution for injection

Intervention Type OTHER

Other Intervention Names

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Matching Placebo

Eligibility Criteria

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Inclusion Criteria

* Written informed consent by participant or legally authorized representative
* Cirrhosis and ascites
* Rapidly progressive worsening in renal function to a serum creatinine (SCr) at least 2.25 mg/dL and meeting a trajectory for SCr to double over 2 weeks
* No sustained improvement in renal function (less than 20% decrease in SCr and SCr at least 2.25 mg/dL) at least 48 hours after diuretic withdrawal and the beginning of plasma volume expansion with albumin
* Discontinues midodrine and octreotide before randomization if applicable

Exclusion Criteria

* Serum creatinine level greater than 7.0 mg/dL
* At least 1 event of large volume paracentesis (LVP) at least 4 L within 2 days of randomization
* Sepsis and/or uncontrolled bacterial infection
* Less than 2 days anti-infective therapy for documented or suspected infection
* Shock
* Being treatment with or exposure to nephrotoxic agents, nonsteroidal anti-inflammatory drugs, or significant radiographic contrast agents (within the last 4 weeks)
* Estimated life expectancy of less than 3 days
* Superimposed acute liver injury due to drugs, dietary supplements, herbal preparations, viral hepatitis, or toxins, with the exception of acute alcoholic hepatitis
* Proteinuria greater than 500 mg/day
* Evidence of obstructive uropathy or parenchymal renal disease on ultrasound or other imaging
* Tubular epithelial casts, heme granular casts, hematuria or microhematuria (greater than 50 red blood cells per high power field in the absence of recent catheterization) on urinalysis
* Pregnancy; all women of child-bearing age and potential must have a negative pregnancy test
* Cardiovascular disease judged by the investigator to be severe
* Current or recent renal replacement therapy (RRT) within the past 4 weeks
* Participation in other clinical research involving investigational medicinal products within 30 days of randomization
* Transjugular intrahepatic portosystemic shunt (TIPS) within 30 days of randomization
* Use of vasopressors for at least 3 consecutive days within the 14-day screening period - patients receiving any vasopressor other than midodrine and octreotide within 24 hours of qualifying SCr are also excluded, ie, a 24-hour washout is required prior to enrollment
* Known allergy or sensitivity to terlipressin or another component of the study treatment
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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Clinical Team Lead

Role: STUDY_DIRECTOR

Mallinckrodt

Locations

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Mayo Clinic - FL

Jacksonville, Florida, United States

Site Status

Jackson Memorial Hospital

Miami, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner Good Samaritan Medical Center

Phoenix, Arizona, United States

Site Status

Mayo Clinic - AZ

Phoenix, Arizona, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

USC Healthcare

Los Angeles, California, United States

Site Status

Stanford Hospital and Clinics

Palo Alto, California, United States

Site Status

UCLA Medical Center

San Diego, California, United States

Site Status

Southern California Research Center

San Diego, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

MedStar Georgetown University Hospital

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

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Tampa General Medical Group

Tampa, Florida, United States

Site Status

Piedmont Hospital Transplant

Atlanta, Georgia, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic - MN

Rochester, Minnesota, United States

Site Status

Saint Louis University

St Louis, Missouri, United States

Site Status

Washington University in St. Louis

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Rutgers New Jersey Medical School

Newark, New Jersey, United States

Site Status

NYU Langone Health

New York, New York, United States

Site Status

Weil Cornell Medical College

New York, New York, United States

Site Status

Mount Sinai Medical Center

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Case Western Reserve Transplant

Cleveland, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

INTEGRIS Baptist Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Drexel University

Philadelphia, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

VA Pittsburgh Healthcare System

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Parkland Health and Hospital System

Dallas, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor Scott and White All Saints Medical Center

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine (St. Luke's)

Houston, Texas, United States

Site Status

Methodist Center for Liver Disease and Transplantation

Houston, Texas, United States

Site Status

Methodist Transplant Hospital

San Antonio, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Medical Center

Charlottesville, Virginia, United States

Site Status

McGuire VA Medical Center

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Harborview Medical Center/Univ. of Washington

Seattle, Washington, United States

Site Status

Swedish Organ Transplant and Liver Center

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre

Vancouver, British Columbia, Canada

Site Status

Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

University of Toronto 9N/983 Toronto General Hospital

Toronto, Ontario, Canada

Site Status

McGill University Health Centre

Montreal, , Canada

Site Status

Centre Hospitalier de l'Université de Montréal

Québec, , Canada

Site Status

Countries

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United States Canada

References

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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)

Wong F, Pappas SC, Curry MP, Reddy KR, Rubin RA, Porayko MK, Gonzalez SA, Mumtaz K, Lim N, Simonetto DA, Sharma P, Sanyal AJ, Mayo MJ, Frederick RT, Escalante S, Jamil K; CONFIRM Study Investigators. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med. 2021 Mar 4;384(9):818-828. doi: 10.1056/NEJMoa2008290.

Reference Type DERIVED
PMID: 33657294 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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MNK19013058

Identifier Type: -

Identifier Source: org_study_id

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