A Phase 3 interventional study of Terlipressin and Placebo in Hepatorenal Syndrome, sponsored by Mallinckrodt. Completed at 73 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-11-29.
Sponsored by Mallinckrodt · Phase 3, Interventional, and Treatment
This study is designed to evaluate the efficacy and safety of intravenous terlipressin versus placebo for the treatment of type 1 hepatorenal syndrome (HRS) in participants receiving standard of care albumin therapy.
Hepatorenal syndrome is a rare syndrome of marked renal dysfunction in patients with cirrhosis, decompensated liver disease, and portal hypertension. Hepatorenal syndrome type 1 is characterized by a rapid progressive renal impairment and has a very poor prognosis with > 80% mortality within 3 months. At present, there are no approved drug therapies for HRS type 1 in the US, Australia, or Canada. The only curative treatment for HRS type 1 and the underlying end-stage cirrhosis is liver transplantation. However, many patients will not survive long enough to receive a liver transplant and therapy, which may provide a bridge to transplantation, is badly needed. Increased understanding of the pathophysiology of HRS type 1 has demonstrated that vasoconstrictive drug therapy may reverse HRS type 1. Substantial data available from many published clinical investigations in the literature provide compelling evidence suggesting that administration of terlipressin improves renal function in patients with HRS.
50 studies on the registry are indexed under Hepatorenal Syndrome; 7 are open to participants now.
This study's enrollment of 196 is above the median of 50 across 36 interventional studies indexed under Hepatorenal Syndrome.
Browse Hepatorenal Syndrome studies →Mallinckrodt is the lead sponsor of 87 studies on the registry; none are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 15 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Rapidly progressive reduction in renal function characterized by:
Note: Albumin doses recommended by the International Ascites Club (IAC) are 1 g/kg on the first day (Maximum 100 g) and 20 - 40 g/day thereafter as clinically indicated. It is recommended (if clinically appropriate) that the albumin dose is kept constant during the study drug administration period.
Note: The qualifying SCr value is the SCr value at least 48 hrs after both diuretic withdrawal (if applicable) and the beginning of albumin fluid challenge. The qualifying SCr value must be ≥ 2.25 mg/dL AND at least 80% of the diagnostic (pre-fluid challenge) SCr value.
Exclusion Criteria:
Sepsis or systemic inflammatory response syndrome (SIRS)
Note: SIRS: Presence of 2 or more of the following findings:
Temperature > 38°C or \< 36°C; heart rate > 90/min; respiratory rate of > 20/min or a PaCO2 of \< 32 mm Hg; white blood cell count of > 12,000 cells/µL or \< 4,000/ µL.
Note: Sepsis: Documented infection and systemic inflammatory response syndrome.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Terlipressin
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.
Drug: Placebo
Each 6 mL vial contains 1 mg lyophilized terlipressin acetate and 10 mg mannitol in sterile 0.9% sodium chloride solution.
Also known as: Lucassin®
11 mg mannitol reconstituted with 5 ml of sterile 0.9% sodium chloride solution.
Also known as: Saline
Percentage of Participants With Confirmed Hepatorenal Syndrome (HRS) Reversal
Confirmed HRS Reversal: The percentage of participants with two serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 48 hours apart, on treatment, and without intervening renal replacement therapy or liver transplant.
Time frame: within 14 days
Percentage of Participants With HRS Reversal
HRS reversal is defined as at least one SCr value of ≤ 1.5 mg/dL on treatment (up to 24 hours after the last dose of study medication).
Time frame: within 14 days
Percentage of Participants With Transplant-free Survival
Transplant-Free Survival up to 90 days, defined as the time (in days) that each participant survives without liver transplantation from the day of randomization.
Time frame: Up to 90 days
Percentage of Participants With Overall Survival
Overall Survival up to 90 days, defined as the time (in days) that each participant survives from the day of randomization.
Time frame: Up to 90 days
Percentage of Participants With Serious Adverse Events
Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments which qualified for the definition of serious adverse event are reported.
Time frame: Up to 30 days post treatment (within 44 days)
The study was conducted at 52 active sites in the United States and Canada.
| Milestone | Terlipressin | Placebo |
|---|---|---|
| Started | 97 | 99 |
| Intent to treat (itt) | 97 | 99 |
| Safety population (treated participants) | 93 | 95 |
| Completed | 52 | 48 |
| Not completed | 45 | 51 |
| Withdrew: Adverse event | 24 | 28 |
| Withdrew: Participant withdrew informed consent | 2 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Death | 16 | 15 |
| Withdrew: Reason not specified | 3 | 5 |
Confirmed HRS Reversal: The percentage of participants with two serum creatinine (SCr) values of ≤ 1.5 mg/dL at least 48 hours apart, on treatment, and without intervening renal replacement therapy or liver transplant.
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Confirmed Hepatorenal Syndrome (HRS) Reversal | 19.6 | 13.1 |
HRS reversal is defined as at least one SCr value of ≤ 1.5 mg/dL on treatment (up to 24 hours after the last dose of study medication).
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With HRS Reversal | 23.7 | 15.2 |
Transplant-Free Survival up to 90 days, defined as the time (in days) that each participant survives without liver transplantation from the day of randomization.
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Transplant-free Survival | 30.9 | 26.3 |
Overall Survival up to 90 days, defined as the time (in days) that each participant survives from the day of randomization.
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Overall Survival | 57.7 | 54.5 |
Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments which qualified for the definition of serious adverse event are reported.
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Serious Adverse Events | 66.7 | 62.1 |
Collected over All-cause mortality was reported for the ITT population. SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment (up to approximately 44 days); deaths are collected through study completion at 90 days from treatment start. Other adverse events were collected up to 7 days of treatment.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Terlipressin | 41/97 (42.3%) | 62/93 (66.7%) | 87/93 (93.5%) |
| Placebo | 45/99 (45.5%) | 59/95 (62.1%) | 82/95 (86.3%) |
| Event | Terlipressin | Placebo |
|---|---|---|
| Multiple Organ Dysfunction SyndromeGeneral disorders | 12/93 | 6/95 |
| Chronic Hepatic FailureHepatobiliary disorders | 9/93 | 8/95 |
| Hepatorenal SyndromeHepatobiliary disorders | 7/93 | 2/95 |
| Respiratory FailureRespiratory, thoracic and mediastinal disorders | 6/93 | 1/95 |
| Hepatic FailureHepatobiliary disorders | 4/93 | 6/95 |
| Abdominal PainGastrointestinal disorders | 5/93 | 1/95 |
| PneumoniaInfections and infestations | 2/93 | 5/95 |
| SepsisInfections and infestations | 4/93 | 3/95 |
| Septic ShockInfections and infestations | 4/93 | 2/95 |
| Cardiac ArrestCardiac disorders | 0/93 | 4/95 |
| Event | Terlipressin | Placebo |
|---|---|---|
| Abdominal painGastrointestinal disorders | 26/93 | 21/95 |
| DiarrhoeaGastrointestinal disorders | 22/93 | 4/95 |
| HypotensionVascular disorders | 17/93 | 7/95 |
| NauseaGastrointestinal disorders | 12/93 | 12/95 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 12/93 | 8/95 |
| HypokalaemiaMetabolism and nutrition disorders | 11/93 | 5/95 |
| Hepatic encephalopathyNervous system disorders | 8/93 | 11/95 |
| AnaemiaBlood and lymphatic system disorders | 10/93 | 9/95 |
| Metabolic acidosisMetabolism and nutrition disorders | 10/93 | 7/95 |
| BradycardiaCardiac disorders | 9/93 | 2/95 |
ITT population.
| Age, Continuous(years) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Mean | 55.8 ± 8.38 | 54.8 ± 8.50 | 55.3 ± 8.43 |
| Sex: Female, Male(Participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Female | 45 | 32 | 77 |
| Male | 52 | 67 | 119 |
| Ethnicity (NIH/OMB)(Participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 10 | 15 | 25 |
| Not Hispanic or Latino | 86 | 84 | 170 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 1 | 2 |
| Asian | 3 | 0 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 7 | 6 | 13 |
| White | 85 | 92 | 177 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Region of Enrollment(participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Canada | 5 | 4 | 9 |
| United States | 92 | 95 | 187 |
Plan to share: 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.
This study is completed, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Terlipressin