A Phase 3 interventional study of Terlipressin and Placebo in Hepatorenal Syndrome, sponsored by Mallinckrodt. Completed at 64 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 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.
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.
50 studies on the registry are indexed under Hepatorenal Syndrome; 7 are open to participants now.
This study's enrollment of 300 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.
Exclusion Criteria:
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.
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.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
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.
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.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
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.
Other: Placebo
Terlipressin solution for injection
Matching placebo solution for injection
Also known as: Matching Placebo
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
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
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
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
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
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
The study was conducted at 60 active sites in the United States and Canada
| Milestone | Terlipressin | Placebo |
|---|---|---|
| Started | 199 | 101 |
| Intent to treat (itt) | 199 | 101 |
| Safety analysis set (sas) | 200 | 99 |
| Systemic inflammatory response syndrome (sirs) subgroup | 84 | 48 |
| Completed | 87 | 52 |
| Not completed | 112 | 49 |
| Withdrew: Death | 101 | 45 |
| Withdrew: Withdrawal by subject | 4 | 2 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Various reasons | 6 | 2 |
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 | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Verified HRS Reversal | 29.1 | 15.8 |
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
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis | 91.3 | 94.4 |
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 | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With HRS Reversal | 36.2 | 16.8 |
Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Durable HRS Reversal | 31.7 | 15.8 |
Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage pf Participants in the SIRS Subgroup With HRS Reversal | 33.3 | 6.3 |
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
| percentage of participants | Terlipressin | Placebo |
|---|---|---|
| Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30 | 24.1 | 15.8 |
Collected over SAEs are collected in the safety analysis set (SAS) from informed consent to 30 days post-treatment; deaths are collected through study completion at 90 days from treatment start. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Terlipressin | 101/200 (50.5%) | 142/200 (71%) | 157/200 (78.5%) |
| Placebo | 45/99 (45.5%) | 62/99 (62.6%) | 82/99 (82.8%) |
| Event | Terlipressin | Placebo |
|---|---|---|
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 21/200 | 3/99 |
| Hepatic failureHepatobiliary disorders | 11/200 | 10/99 |
| Chronic hepatic failureHepatobiliary disorders | 14/200 | 8/99 |
| Multiple organ dysfunction syndromeGeneral disorders | 11/200 | 5/99 |
| Abdominal painGastrointestinal disorders | 10/200 | 1/99 |
| SepsisInfections and infestations | 10/200 | 0/99 |
| Hepatic encephalopathyNervous system disorders | 9/200 | 3/99 |
| Gastrointestinal haemorrhageGastrointestinal disorders | 8/200 | 0/99 |
| Hepatic cirrhosisHepatobiliary disorders | 8/200 | 3/99 |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 8/200 | 2/99 |
| Event | Terlipressin | Placebo |
|---|---|---|
| Abdominal painGastrointestinal disorders | 38/200 | 5/99 |
| NauseaGastrointestinal disorders | 32/200 | 10/99 |
| DiarrhoeaGastrointestinal disorders | 26/200 | 7/99 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 24/200 | 5/99 |
| Hepatic encephalopathyNervous system disorders | 17/200 | 11/99 |
| VomitingGastrointestinal disorders | 17/200 | 9/99 |
| TachycardiaCardiac disorders | 10/200 | 8/99 |
| HypotensionVascular disorders | 16/200 | 6/99 |
| Fluid overloadMetabolism and nutrition disorders | 15/200 | 3/99 |
| HypokalaemiaMetabolism and nutrition disorders | 15/200 | 7/99 |
Intent to treat (ITT) population
| Age, Continuous(years) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Mean | 54.0 ± 11.34 | 53.6 ± 11.83 | 53.8 ± 11.49 |
| Sex: Female, Male(Participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Female | 79 | 42 | 121 |
| Male | 120 | 59 | 179 |
| Ethnicity (NIH/OMB)(Participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 32 | 13 | 45 |
| Not Hispanic or Latino | 165 | 88 | 253 |
| Unknown or Not Reported | 2 | 0 | 2 |
| Race (NIH/OMB)(Participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 2 | 0 | 2 |
| Asian | 5 | 1 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 12 | 5 | 17 |
| White | 177 | 94 | 271 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 3 | 1 | 4 |
| Region of Enrollment(participants) | Terlipressin | Placebo | Total |
|---|---|---|---|
| Canada | 21 | 12 | 33 |
| United States | 178 | 89 | 267 |
PDFs hosted by the registry, ClinicalTrials.gov.
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.
Ran from Jul 2016 to primary completion in Jul 2019, 36 months.
Results were first posted in Aug 2022, 3 years after primary completion. A results delay was requested in May 2020.
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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