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Hepatorenal SyndromePhase 3NCT02770716

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

A Phase 3 study testing Terlipressin in people with Hepatorenal Syndrome, run by Mallinckrodt at 64 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatorenal Syndrome
What is being tested?
Terlipressin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
300 participants
Where
64 sitesin 2 countries
Study dates
13 Jul 2016to 24 Jul 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 18Show fewer
  • 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

Trial locations and contacts

64 sites in 2 countries.

64 sites in 2 countries

United States59 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Piedmont Hospital Transplant

    Atlanta, Georgia, 30309

  • Emory University Hospital

    Atlanta, Georgia, 30329

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Medical Center

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Case Western Reserve Transplant

    Cleveland, Ohio, 44106

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Parkland Health and Hospital System

    Dallas, Texas, 75235

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Baylor Scott and White All Saints Medical Center

    Fort Worth, Texas, 76104

  • University of Florida

    Gainesville, Florida, 32610

  • Baylor College of Medicine (St. Luke's)

    Houston, Texas, 77030

  • Methodist Center for Liver Disease and Transplantation

    Houston, Texas, 77030

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

  • Mayo Clinic - FL

    Jacksonville, Florida, 32224

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • USC Healthcare

    Los Angeles, California, 90033

  • Jackson Memorial Hospital

    Miami, Florida, 33136

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • NYU Langone Health

    New York, New York, 10016

  • Weil Cornell Medical College

    New York, New York, 10021

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Rutgers New Jersey Medical School

    Newark, New Jersey, 07102

  • INTEGRIS Baptist Medical Center

    Oklahoma City, Oklahoma, 73112

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Stanford Hospital and Clinics

    Palo Alto, California, 94305

  • Drexel University

    Philadelphia, Pennsylvania, 19102

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Banner Good Samaritan Medical Center

    Phoenix, Arizona, 85006

  • Mayo Clinic - AZ

    Phoenix, Arizona, 85057

  • VA Pittsburgh Healthcare System

    Pittsburgh, Pennsylvania, 15240

  • McGuire VA Medical Center

    Richmond, Virginia, 23245

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Mayo Clinic - MN

    Rochester, Minnesota, 55902

  • University of Utah

    Salt Lake City, Utah, 84132

  • Methodist Transplant Hospital

    San Antonio, Texas, 78229

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCLA Medical Center

    San Diego, California, 90095

  • Southern California Research Center

    San Diego, California, 92118

  • California Pacific Medical Center

    San Francisco, California, 94115

  • Harborview Medical Center/Univ. of Washington

    Seattle, Washington, 98104

  • Swedish Organ Transplant and Liver Center

    Seattle, Washington, 98104

  • University of Washington

    Seattle, Washington, 98105

  • Saint Louis University

    St Louis, Missouri, 63110

  • Washington University in St. Louis

    St Louis, Missouri, 63110

  • Tampa General Medical Group

    Tampa, Florida, 33606

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • University of Arizona

    Tucson, Arizona, 85724

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

Canada5 sites

  • McGill University Health Centre

    Montreal, H4A3J1

  • Ottawa Hospital

    Ottawa, Ontario, K1H 8L6

  • Centre Hospitalier de l'Université de Montréal

    Québec, H2X3J4

  • University of Toronto 9N/983 Toronto General Hospital

    Toronto, Ontario, M5G2C4

  • Vancouver General Hospital, Gordon and Leslie Diamond Health Care Centre

    Vancouver, British Columbia, V5Z IM9

Other trials in Canada

About this study

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)

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.

Read the 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.

Being tested
Terlipressin, Placebo
Keywords
Type 1
Medical subject headings
Hepatorenal Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TerlipressinDrug

    Terlipressin solution for injection

  • PlaceboOther

    Also called Matching Placebo

    Matching placebo solution for injection

Study groups in NCT02770716
Study groupRoleWhat they receive
TerlipressinExperimentalParticipants 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.
Receives: Drug: Terlipressin
PlaceboPlacebo 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.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: within 15 Days

  2. 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

    Measured: within 25 days

Secondary outcomes (4)

  1. 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

    Measured: within 14 days

  2. Percentage of Participants With Durable HRS Reversal

    Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30

    Measured: Day 30

  3. 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

    Measured: within 14 days

  4. 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

    Measured: Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2016 (estimated)
  2. Study start13 Jul 2016
  3. Primary completion24 Jul 2019
  4. Study completion24 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
300 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02770716
Sponsor's protocol ID
MNK19013058
Status last verified
Nov 2022
First submitted
10 May 2016
Last updated
29 Nov 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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.

Publications

  • 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.

    PubMed 41200852

  • Bajaj 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.

    PubMed 40704461

  • Allegretti AS, Levitsky J, Sharma P, Ouyang T, Jamil K, Silvey S, Bajaj JS. Predictors of response to terlipressin therapy in hepatorenal syndrome: Metabolomic and proteomic analysis from the CONFIRM trial. Hepatol Commun. 2025 Jul 14;9(8):e0766. doi: 10.1097/HC9.0000000000000766. eCollection 2025 Aug 1.

    PubMed 40658810

  • Mujtaba 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.

    PubMed 37302573

  • Velez 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.

    PubMed 37143199

  • Curry 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.

    PubMed 36633470

  • 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.

    PubMed 33657294

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Terlipressin in people with Hepatorenal Syndrome, run by Mallinckrodt at 64 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Verified HRS Reversal (time frame: within 15 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02770716, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2022.

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