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

Conditions

Hepatorenal Syndrome

Keywords

Type 1

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.

Rockey DC, Gordon F, Thuluvath PJ, Victor D, Kemmer N, Cardoza S, Jamil K, Frederick RT.

2025-12-013 citations

10.1111/liv.70399

Bradycardia and Other Arrhythmias in Patients With Hepatorenal Syndrome‐Acute Kidney Injury Following Terlipressin Treatment: A Pooled Analysis of Three North American Phase <scp>III</scp> Clinical Studies

Jasmohan S. Bajaj, Paul Y. Kwo, S. Chris Pappas, Jacqueline O'leary, Khurram Jamil et al. (7 authors)

Alimentary Pharmacology & Therapeutics2025-07-243 citations

10.1111/apt.70297

Decreased need for RRT in liver transplant recipients after pretransplant treatment of hepatorenal syndrome-type 1 with terlipressin

Ethan M. Weinberg, Florence Wong, Hugo E. Vargas, Michael P. Curry, Khurram Jamil et al. (8 authors)

Liver Transplantation2023-10-069 citations

10.1097/lvt.0000000000000277

S1477 The Effect of Terlipressin on Blood Pressure, Mean Arterial Pressure, and Heart Rate in Patients with Hepatorenal Syndrome: A Post Hoc Analysis of the CONFIRM Study

Jacqueline G. O’Leary, Nicholas Lim, Mark Wong, David A. Sass, Sujit Janardhan et al. (7 authors)

The American Journal of Gastroenterology2023-10-01

10.14309/01.ajg.0000955548.19564.9e

Terlipressin in combination with albumin as a therapy for hepatorenal syndrome in patients aged 65 years or older.

Mujtaba MA, Gamilla-Crudo AK, Merwat SN, Hussain SA, Kueht M, Karim A, Khattak MW, Rooney PJ, Jamil K.

2023-06-101 citations

10.1016/j.aohep.2023.101126

Terlipressin Treatment Is Associated With Reversal of Hepatorenal Syndrome in Patients With Alcoholic Hepatitis

Samuel H. Sigal, Arun J. Sanyal, R. Todd Frederick, Ethan M. Weinberg, S. Chris Pappas et al. (6 authors)

Clinical Gastroenterology and Hepatology2023-02-267 citations

10.1016/j.cgh.2023.02.015

S1173 Terlipressin Treatment of Patients With Hepatorenal Syndrome Type 1 Decreased the Need for Renal Replacement Therapy in Transplant Recipients: A 12-Month Follow-Up of the CONFIRM Study

Khurram Jamil, Ethan M. Weinberg, K. Rajender Reddy

The American Journal of Gastroenterology2022-10-011 citations

10.14309/01.ajg.0000861332.82608.85

Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome

Florence Wong, S. Chris Pappas, Michael P. Curry, K. Rajender Reddy, Raymond A. Rubin et al. (16 authors)

New England Journal of Medicine2021-03-03418 citations

10.1056/nejmoa2008290

<p>Verified Hepatorenal Syndrome Reversal As A Robust Multi-Component Primary End Point: The CONFIRM Study Trial Design</p>

Khurram Jamil, S. Chris Pappas, Florence Wong, Arun J. Sanyal

Open Access Journal of Clinical Trials2019-11-012 citations

10.2147/oajct.s224974

Interventions

DRUGTerlipressin

Terlipressin solution for injection

OTHERPlacebo

Matching placebo solution for injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Verified HRS Reversal	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	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

Measure	Time frame	Description
Percentage of Participants With HRS Reversal	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	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	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	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

Countries

Canada, United States

Participant flow

Recruitment details

The study was conducted at 60 active sites in the United States and Canada

Participants by arm

Arm	Count
Terlipressin Participants 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.	199
Placebo Participants 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.	101
Total	300

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	101	45
Overall Study	Lost to Follow-up	1	0
Overall Study	Various reasons	6	2
Overall Study	Withdrawal by Subject	4	2

Baseline characteristics

Characteristic	Terlipressin	Total	Placebo
Age, Continuous	54.0 years STANDARD_DEVIATION 11.34	53.8 years STANDARD_DEVIATION 11.49	53.6 years STANDARD_DEVIATION 11.83
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants	45 Participants	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	165 Participants	253 Participants	88 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	6 Participants	1 Participants
Race (NIH/OMB) Black or African American	12 Participants	17 Participants	5 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants	4 Participants	1 Participants
Race (NIH/OMB) White	177 Participants	271 Participants	94 Participants
Region of Enrollment Canada	21 participants	33 participants	12 participants
Region of Enrollment United States	178 participants	267 participants	89 participants
Sex: Female, Male Female	79 Participants	121 Participants	42 Participants
Sex: Female, Male Male	120 Participants	179 Participants	59 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	101 / 200	45 / 99
other Total, other adverse events	157 / 200	82 / 99
serious Total, serious adverse events	142 / 200	62 / 99

Outcome results

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

Time frame: within 25 days

Population: ITT

Arm	Measure	Value (NUMBER)
Terlipressin	Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis	91.3 percentage of participants
Placebo	Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis	94.4 percentage of participants

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.

Time frame: within 15 Days

Population: ITT

Arm	Measure	Value (NUMBER)
Terlipressin	Percentage of Participants With Verified HRS Reversal	29.1 percentage of participants
Placebo	Percentage of Participants With Verified HRS Reversal	15.8 percentage of participants

Secondary

Percentage of Participants With Durable HRS Reversal

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

Time frame: Day 30

Population: ITT

Arm	Measure	Value (NUMBER)
Terlipressin	Percentage of Participants With Durable HRS Reversal	31.7 percentage of participants
Placebo	Percentage of Participants With Durable HRS Reversal	15.8 percentage of participants

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

Time frame: within 14 days

Population: ITT

Arm	Measure	Value (NUMBER)
Terlipressin	Percentage of Participants With HRS Reversal	36.2 percentage of participants
Placebo	Percentage of Participants With HRS Reversal	16.8 percentage of participants

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

Time frame: Day 30

Population: ITT

Arm	Measure	Value (NUMBER)
Terlipressin	Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30	24.1 percentage of participants
Placebo	Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30	15.8 percentage of participants

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

Time frame: within 14 days

Population: ITT participants in the SIRS subgroup

Arm	Measure	Value (NUMBER)
Terlipressin	Percentage pf Participants in the SIRS Subgroup With HRS Reversal	33.3 percentage of participants
Placebo	Percentage pf Participants in the SIRS Subgroup With HRS Reversal	6.3 percentage of participants

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis

Percentage of Participants With Verified HRS Reversal

Percentage of Participants With Durable HRS Reversal

Percentage of Participants With HRS Reversal

Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30

Percentage pf Participants in the SIRS Subgroup With HRS Reversal