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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02770716
Other study ID # MNK19013058
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date July 13, 2016
Est. completion date July 24, 2019

Study information

Verified date November 2022
Source Mallinckrodt
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 300
Est. completion date July 24, 2019
Est. primary completion date July 24, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Terlipressin
Terlipressin solution for injection
Other:
Placebo
Matching placebo solution for injection

Locations

Country Name City State
Canada McGill University Health Centre Montréal
Canada Ottawa Hospital Ottawa Ontario
Canada Centre Hospitalier de l'Université de Montréal Québec
Canada University of Toronto 9N/983 Toronto General Hospital Toronto Ontario
Canada Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre Vancouver British Columbia
United States University of Michigan Medical Center Ann Arbor Michigan
United States Emory University Hospital Atlanta Georgia
United States Piedmont Hospital Transplant Atlanta Georgia
United States Mercy Medical Center Baltimore Maryland
United States University of Alabama at Birmingham Birmingham Alabama
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Montefiore Medical Center Bronx New York
United States Medical University of South Carolina Charleston South Carolina
United States University of Virginia Medical Center Charlottesville Virginia
United States Northwestern University Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States Case Western Reserve Transplant Cleveland Ohio
United States The Ohio State University Wexner Medical Center Columbus Ohio
United States Baylor University Medical Center Dallas Texas
United States Parkland Health and Hospital System Dallas Texas
United States UT Southwestern Medical Center Dallas Texas
United States Baylor Scott and White All Saints Medical Center Fort Worth Texas
United States University of Florida Gainesville Florida
United States Baylor College of Medicine (St. Luke's) Houston Texas
United States Methodist Center for Liver Disease and Transplantation Houston Texas
United States University of Iowa Hospitals & Clinics Iowa City Iowa
United States Mayo Clinic - FL Jacksonville Florida
United States University of Kansas Medical Center Kansas City Kansas
United States USC Healthcare Los Angeles California
United States Jackson Memorial Hospital Miami Florida
United States University of Miami Miami Florida
United States University of Minnesota Minneapolis Minnesota
United States Vanderbilt University Medical Center Nashville Tennessee
United States Ochsner Clinic Foundation New Orleans Louisiana
United States Mount Sinai Medical Center New York New York
United States NYU Langone Health New York New York
United States Weil Cornell Medical College New York New York
United States Rutgers New Jersey Medical School Newark New Jersey
United States INTEGRIS Baptist Medical Center Oklahoma City Oklahoma
United States University of Nebraska Medical Center Omaha Nebraska
United States Stanford Hospital and Clinics Palo Alto California
United States Drexel University Philadelphia Pennsylvania
United States Hospital of the University of Pennsylvania Philadelphia Pennsylvania
United States Jefferson University Philadelphia Pennsylvania
United States Banner Good Samaritan Medical Center Phoenix Arizona
United States Mayo Clinic - AZ Phoenix Arizona
United States VA Pittsburgh Healthcare System Pittsburgh Pennsylvania
United States McGuire VA Medical Center Richmond Virginia
United States Virginia Commonwealth University Richmond Virginia
United States Mayo Clinic - MN Rochester Minnesota
United States Saint Louis University Saint Louis Missouri
United States Washington University in St. Louis Saint Louis Missouri
United States University of Utah Salt Lake City Utah
United States Methodist Transplant Hospital San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Southern California Research Center San Diego California
United States UCLA Medical Center San Diego California
United States California Pacific Medical Center San Francisco California
United States Harborview Medical Center/Univ. of Washington Seattle Washington
United States Swedish Organ Transplant and Liver Center Seattle Washington
United States University of Washington Seattle Washington
United States Tampa General Medical Group Tampa Florida
United States University of Arizona Tucson Arizona
United States MedStar Georgetown University Hospital Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Mallinckrodt

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With Verified HRS Reversal Defined as the percentage of participants with 2 consecutive SCr values = 1.5 mg/dL at least 2 hours apart, while on treatment by Day 14 or discharge (on treatment defined as up to 24 hours after the final dose of study drug), per protocol. within 15 Days
Primary Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis Defined as the percentage of participants with verified HRS reversal who lived at least 10 days without RRT, and were otherwise viable (per protocol) for inclusion in the primary endpoint analysis within 25 days
Secondary Percentage of Participants With HRS Reversal Defined as the percentage of participants with a SCr value no more than 1.5 mg/dL by Day 14 or discharge, and were viable (per protocol) for inclusion in the secondary endpoint analysis within 14 days
Secondary Percentage of Participants With Durable HRS Reversal Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30 Day 30
Secondary Percentage pf Participants in the SIRS Subgroup With HRS Reversal Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge within 14 days
Secondary Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30 Defined as the percentage of participants who had achieved verified HRS reversal by Day 15 or discharge and did not revert to baseline measures by day 30 Day 30
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