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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02770716
Recruitment Status : Completed
First Posted : May 12, 2016
Results First Posted : August 18, 2022
Last Update Posted : November 29, 2022
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

Study Description
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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.


Condition or disease Intervention/treatment Phase
Hepatorenal Syndrome Drug: Terlipressin Other: Placebo Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 13, 2016
Actual Primary Completion Date : July 24, 2019
Actual Study Completion Date : July 24, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Terlipressin
Terlipressin solution for injection
Placebo Comparator: 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.
 Other: Placebo
Matching placebo solution for injection
Other Name: Matching Placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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 Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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 Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02770716


Locations
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Sponsors and Collaborators
Mallinckrodt
Investigators
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Study Director: Clinical Team Lead Mallinckrodt
  Study Documents (Full-Text)

Documents provided by Mallinckrodt:
Study Protocol and Statistical Analysis Plan  [PDF] October 2, 2018

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT02770716    
Other Study ID Numbers: MNK19013058
First Posted: May 12, 2016    Key Record Dates
Results First Posted: August 18, 2022
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mallinckrodt:
Type 1
Additional relevant MeSH terms:
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Terlipressin
Hepatorenal Syndrome
Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Kidney Diseases
 Urologic Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Antihypertensive Agents
Vasoconstrictor Agents