Current partner codePEPTIDESDE
NCT02770716·Phase 3·INTERVENTIONAL

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

Status

Completed

Phase

Phase 3

Enrollment

300

Locations

64

Results

Posted

Publications

6

Study summary

What the protocol is testing.

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.

Full 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.

Interventions

Treatment arms and agents.

DRUG

Terlipressin

Terlipressin solution for injection

OTHER

Placebo

Matching placebo solution for injection

Timeline

From registration to results.

  1. First posted

    May 12, 2016

  2. Study start

    Jul 13, 2016

  3. Primary completion

    Jul 24, 2019

  4. Study completion

    Jul 24, 2019

  5. Results posted

    Aug 18, 2022

  6. Registry updated

    Nov 29, 2022

Outcomes

What the study measures.

Primary outcomes

Percentage of Participants With Verified HRS Reversal

Time frame · within 15 Days

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.

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 endpoint analysis

Secondary outcomes

Percentage 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

Percentage of Participants With Durable HRS Reversal

Time frame · Day 30

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

Percentage pf Participants in the SIRS Subgroup With HRS Reversal

Time frame · within 14 days

Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge

Percentage of Participants With 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

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
Not reported
Sex
ALL
Healthy volunteers
No

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

Study locations

64 registered sites.

Canada · United States. Showing up to 24 locations stored in the fast local snapshot.

University of Alabama at Birmingham

Birmingham, Alabama, United States

Banner Good Samaritan Medical Center

Phoenix, Arizona, United States

Mayo Clinic - AZ

Phoenix, Arizona, United States

University of Arizona

Tucson, Arizona, United States

USC Healthcare

Los Angeles, California, United States

Stanford Hospital and Clinics

Palo Alto, California, United States

UCLA Medical Center

San Diego, California, United States

Southern California Research Center

San Diego, California, United States

California Pacific Medical Center

San Francisco, California, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

University of Florida

Gainesville, Florida, United States

Mayo Clinic - FL

Jacksonville, Florida, United States

Jackson Memorial Hospital

Miami, Florida, United States

University of Miami

Miami, Florida, United States

Tampa General Medical Group

Tampa, Florida, United States

Piedmont Hospital Transplant

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Mercy Medical Center

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Publications

Results and literature.

PMID 41200852Rockey 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 40704461Bajaj 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 37302573Mujtaba 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 37143199Velez 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 36633470Curry 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 33657294Wong 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.

Primary links

Continue at the source.

Related trials

More studies on Terlipressin.

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