Clinical trial NCT02770716: Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatorenal Syndrome
Keywords: Type 1
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2016-05-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants With Verified HRS Reversal
timeFrame: within 15 Days
measure: Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis
timeFrame: within 25 days
Secondary outcomes:
measure: Percentage of Participants With HRS Reversal
timeFrame: within 14 days
measure: Percentage of Participants With Durable HRS Reversal
timeFrame: Day 30
measure: Percentage pf Participants in the SIRS Subgroup With HRS Reversal
timeFrame: within 14 days
measure: Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30
timeFrame: Day 30
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic - AZ
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: USC Healthcare
state: California
city: Palo Alto
country: United States
facility: Stanford Hospital and Clinics
state: California
city: San Diego
country: United States
facility: UCLA Medical Center
state: California
city: San Diego
country: United States
facility: Southern California Research Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - FL
state: Florida
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: Tampa General Medical Group
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital Transplant
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - MN
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Weil Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve Transplant
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: VA Pittsburgh Healthcare System
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Parkland Health and Hospital System
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott and White All Saints Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine (St. Luke's)
state: Texas
city: Houston
country: United States
facility: Methodist Center for Liver Disease and Transplantation
state: Texas
city: San Antonio
country: United States
facility: Methodist Transplant Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center/Univ. of Washington
state: Washington
city: Seattle
country: United States
facility: Swedish Organ Transplant and Liver Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vancouver
country: Canada
facility: Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto 9N/983 Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre
city: Québec
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
Study officials:
affiliation: Mallinckrodt
name: Clinical Team Lead
role: STUDY_DIRECTOR
References:
citation: 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.