Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1
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)
1 other identifier
interventional
300
2 countries
64
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jul 2016
Typical duration for phase_3
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 10, 2016
CompletedFirst Posted
Study publicly available on registry
May 12, 2016
CompletedStudy Start
First participant enrolled
July 13, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 24, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
July 24, 2019
CompletedResults Posted
Study results publicly available
August 18, 2022
CompletedNovember 29, 2022
November 1, 2022
3 years
May 10, 2016
July 22, 2022
November 4, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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 Outcomes (4)
Percentage of Participants With HRS Reversal
within 14 days
Percentage of Participants With Durable HRS Reversal
Day 30
Percentage pf Participants in the SIRS Subgroup With HRS Reversal
within 14 days
Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30
Day 30
Study Arms (2)
Terlipressin
EXPERIMENTALParticipants 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.
Placebo
PLACEBO COMPARATORParticipants 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mallinckrodtlead
Study Sites (64)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Banner Good Samaritan Medical Center
Phoenix, Arizona, 85006, United States
Mayo Clinic - AZ
Phoenix, Arizona, 85057, United States
University of Arizona
Tucson, Arizona, 85724, United States
USC Healthcare
Los Angeles, California, 90033, United States
Stanford Hospital and Clinics
Palo Alto, California, 94305, United States
UCLA Medical Center
San Diego, California, 90095, United States
Southern California Research Center
San Diego, California, 92118, United States
California Pacific Medical Center
San Francisco, California, 94115, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
University of Florida
Gainesville, Florida, 32610, United States
Mayo Clinic - FL
Jacksonville, Florida, 32224, United States
Jackson Memorial Hospital
Miami, Florida, 33136, United States
University of Miami
Miami, Florida, 33136, United States
Tampa General Medical Group
Tampa, Florida, 33606, United States
Piedmont Hospital Transplant
Atlanta, Georgia, 30309, United States
Emory University Hospital
Atlanta, Georgia, 30329, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Mercy Medical Center
Baltimore, Maryland, 21202, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic - MN
Rochester, Minnesota, 55902, United States
Saint Louis University
St Louis, Missouri, 63110, United States
Washington University in St. Louis
St Louis, Missouri, 63110, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07102, United States
NYU Langone Health
New York, New York, 10016, United States
Weil Cornell Medical College
New York, New York, 10021, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Case Western Reserve Transplant
Cleveland, Ohio, 44106, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
INTEGRIS Baptist Medical Center
Oklahoma City, Oklahoma, 73112, United States
Drexel University
Philadelphia, Pennsylvania, 19102, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Jefferson University
Philadelphia, Pennsylvania, 19107, United States
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, 15240, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Parkland Health and Hospital System
Dallas, Texas, 75235, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
Baylor Scott and White All Saints Medical Center
Fort Worth, Texas, 76104, United States
Baylor College of Medicine (St. Luke's)
Houston, Texas, 77030, United States
Methodist Center for Liver Disease and Transplantation
Houston, Texas, 77030, United States
Methodist Transplant Hospital
San Antonio, Texas, 78229, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
University of Utah
Salt Lake City, Utah, 84132, United States
University of Virginia Medical Center
Charlottesville, Virginia, 22908, United States
McGuire VA Medical Center
Richmond, Virginia, 23245, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Harborview Medical Center/Univ. of Washington
Seattle, Washington, 98104, United States
Swedish Organ Transplant and Liver Center
Seattle, Washington, 98104, United States
University of Washington
Seattle, Washington, 98105, United States
Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre
Vancouver, British Columbia, V5Z IM9, Canada
Ottawa Hospital
Ottawa, Ontario, K1H 8L6, Canada
University of Toronto 9N/983 Toronto General Hospital
Toronto, Ontario, M5G2C4, Canada
McGill University Health Centre
Montreal, H4A3J1, Canada
Centre Hospitalier de l'Université de Montréal
Québec, H2X3J4, Canada
Related Publications (6)
Rockey DC, Gordon F, Thuluvath PJ, Victor D, Kemmer N, Cardoza S, Jamil K, Frederick RT. Terlipressin for Hepatorenal Syndrome in Patients With Early-Stage Acute-on-Chronic Liver Failure. Liver Int. 2025 Dec;45(12):e70399. doi: 10.1111/liv.70399.
PMID: 41200852DERIVEDBajaj 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 Dec;62(11-12):1192-1201. doi: 10.1111/apt.70297. Epub 2025 Jul 24.
PMID: 40704461DERIVEDMujtaba 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.
PMID: 37302573DERIVEDVelez 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.
PMID: 37143199DERIVEDCurry 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.
PMID: 36633470DERIVEDWong 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.
PMID: 33657294DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information Call Center
- Organization
- Mallinckrodt Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Clinical Team Lead
Mallinckrodt
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 10, 2016
First Posted
May 12, 2016
Study Start
July 13, 2016
Primary Completion
July 24, 2019
Study Completion
July 24, 2019
Last Updated
November 29, 2022
Results First Posted
August 18, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will not share
Discussion of statistical endpoints and analysis are included in manuscripts. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT02770716) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.