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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02770716
Recruitment Status : Completed
First Posted : May 12, 2016
Last Update Posted : May 27, 2020
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

Brief 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.


Condition or disease Intervention/treatment Phase
Hepatorenal Syndrome Drug: Terlipressin Other: Placebo Comparator Phase 3

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1 (The CONFIRM Study)
Actual Study Start Date : July 13, 2016
Actual Primary Completion Date : July 24, 2019
Actual Study Completion Date : July 24, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Terlipressin

Participants will receive terlipressin intravenously as a bolus injection over 2 minutes at a dose of 1 mg (1 vial) every 6 hours (+/- 30 minutes), followed by a saline flush.

Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.

Drug: Terlipressin
Each 6 mL vial contains 1 mg lyophilized terlipressin acetate and 10 mg mannitol in sterile 0.9% sodium chloride solution

Placebo Comparator: Placebo

Participants will receive 1 vial of matching placebo intravenously as a bolus injection of 1 vial over 2 minutes every 6 hours (+/- 30 minutes), followed by a saline flush.

Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.

Other: Placebo Comparator
11 mg mannitol reconstituted with 5 ml of sterile 0.9% sodium chloride solution




Primary Outcome Measures :
  1. Verified HRS Reversal [ Time Frame: within 15 Days ]
    Defined as the percentage of participants with 2 consecutive qualified SCr values ≤1.5 mg/dL at least 2 hours apart.

  2. Percentage of participants who were viable (per protocol) for inclusion in the primary end point analysis [ Time Frame: within 25 days ]
    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 end point analysis


Secondary Outcome Measures :
  1. Incidence of participants with HRS reversal [ Time Frame: within 14 days ]
    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

  2. Durability of HRS reversal [ Time Frame: Day 30 ]
    Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30

  3. Incidence of HRS reversal in the systemic inflammatory response syndrome (SIRS) subgroup [ Time Frame: within 14 days ]
    Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge

  4. Incidence of verified HRS reversal without HRS recurrence by Day 30 [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02770716


Locations
Hide Hide 64 study locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
Mayo Clinic - AZ
Phoenix, Arizona, United States, 85057
University of Arizona
Tucson, Arizona, United States, 85724
United States, California
USC Healthcare
Los Angeles, California, United States, 90033
Stanford Hospital and Clinics
Palo Alto, California, United States, 94305
UCLA Medical Center
San Diego, California, United States, 90095
Southern California Research Center
San Diego, California, United States, 92118
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Mayo Clinic - FL
Jacksonville, Florida, United States, 32224
Jackson Memorial Hospital
Miami, Florida, United States, 33136
University of Miami
Miami, Florida, United States, 33136
Tampa General Medical Group
Tampa, Florida, United States, 33606
United States, Georgia
Piedmont Hospital Transplant
Atlanta, Georgia, United States, 30309
Emory University Hospital
Atlanta, Georgia, United States, 30329
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Iowa
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Mayo Clinic - MN
Rochester, Minnesota, United States, 55902
United States, Missouri
Saint Louis University
Saint Louis, Missouri, United States, 63110
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Rutgers New Jersey Medical School
Newark, New Jersey, United States, 07102
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
NYU Langone Health
New York, New York, United States, 10016
Weil Cornell Medical College
New York, New York, United States, 10021
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Ohio
Case Western Reserve Transplant
Cleveland, Ohio, United States, 44106
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
United States, Oklahoma
INTEGRIS Baptist Medical Center
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
Drexel University
Philadelphia, Pennsylvania, United States, 19102
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Jefferson University
Philadelphia, Pennsylvania, United States, 19107
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, United States, 15240
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Parkland Health and Hospital System
Dallas, Texas, United States, 75235
Baylor University Medical Center
Dallas, Texas, United States, 75246
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor Scott and White All Saints Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine (St. Luke's)
Houston, Texas, United States, 77030
Methodist Center for Liver Disease and Transplantation
Houston, Texas, United States, 77030
Methodist Transplant Hospital
San Antonio, Texas, United States, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
University of Virginia Medical Center
Charlottesville, Virginia, United States, 22908
McGuire VA Medical Center
Richmond, Virginia, United States, 23245
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
Harborview Medical Center/Univ. of Washington
Seattle, Washington, United States, 98104
Swedish Organ Transplant and Liver Center
Seattle, Washington, United States, 98104
University of Washington
Seattle, Washington, United States, 98105
Canada, British Columbia
Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
Vancouver, British Columbia, Canada, V5Z IM9
Canada, Ontario
Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
University of Toronto 9N/983 Toronto General Hospital
Toronto, Ontario, Canada, M5G2C4
Canada
McGill University Health Centre
Montréal, Canada, H4A3J1
Centre Hospitalier de l'Université de Montréal
Québec, Canada, H2X3J4
Sponsors and Collaborators
Mallinckrodt
Investigators
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Study Director: Clinical Team Lead Mallinckrodt
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Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT02770716    
Other Study ID Numbers: MNK19013058
First Posted: May 12, 2016    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mallinckrodt:
Type 1
Additional relevant MeSH terms:
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Hepatorenal Syndrome
Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Kidney Diseases
Urologic Diseases
Terlipressin
Antihypertensive Agents
Vasoconstrictor Agents