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Study To Confirm Efficacy and Safety of Terlipressin in HRS Type 1

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ClinicalTrials.gov Identifier: NCT02770716
Recruitment Status : Completed
First Posted : May 12, 2016
Last Update Posted : August 14, 2019
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

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 Comparator 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.

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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


Arm Intervention/treatment
Experimental: Terlipressin

Participants will receive terlipressin intravenously as a bolus injection over 2 minutes at a dose of 1 mg (1 vial) every 6 hours (+/- 30 minutes), followed by a saline flush.

Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.

Drug: Terlipressin
Each 6 mL vial contains 1 mg lyophilized terlipressin acetate and 10 mg mannitol in sterile 0.9% sodium chloride solution
Other Name: Experimental product

Placebo Comparator: Placebo

Participants will receive 1 vial of matching placebo intravenously as a bolus injection of 1 vial over 2 minutes every 6 hours (+/- 30 minutes), followed by a saline flush.

Dose, duration, retreatment and/or discontinuation may be modified by the investigator, per protocol.

Other: Placebo Comparator
11 mg mannitol reconstituted with 5 ml of sterile 0.9% sodium chloride solution
Other Name: Reference product




Primary Outcome Measures :
  1. Verified HRS Reversal [ Time Frame: within 15 Days ]
    Defined as the percentage of participants with 2 consecutive qualified SCr values ≤1.5 mg/dL at least 2 hours apart.

  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 end point analysis


Secondary Outcome Measures :
  1. Incidence 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. Durability of HRS reversal [ Time Frame: Day 30 ]
    Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30

  3. Incidence of HRS reversal in the systemic inflammatory response syndrome (SIRS) subgroup [ Time Frame: within 14 days ]
    Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge

  4. Incidence of 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



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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

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


  Show 64 Study Locations
Sponsors and Collaborators
Mallinckrodt
Investigators
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Study Director: Clinical Team Lead Mallinckrodt

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Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT02770716     History of Changes
Other Study ID Numbers: MNK19013058
First Posted: May 12, 2016    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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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Hepatorenal Syndrome
Syndrome
Disease
Pathologic Processes
Liver Diseases
Digestive System Diseases
Kidney Diseases
Urologic Diseases
Terlipressin
Antihypertensive Agents
Vasoconstrictor Agents