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

Hepatorenal Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02770716
• Other study ID #: MNK19013058
• Status: Completed
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Hepatorenal Syndrome
• Syndrome

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