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.
Out of every three participants, two will receive terlipressin and one will receive placebo.
Assignments will be made randomly.
Brief Title
Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1
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.
Completion Date
Completion Date Type
Actual
Conditions
Hepatorenal Syndrome
Eligibility 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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Type 1
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02770716
Org Class
Industry
Org Full Name
Mallinckrodt
Org Study Id
MNK19013058
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percentage of Participants With Verified HRS Reversal
Outcome Time Frame
within 15 Days
Outcome Description
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
Outcome Measure
Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis
Outcome Time Frame
within 25 days
Secondary Outcomes
Outcome Description
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
Outcome Time Frame
within 14 days
Outcome Measure
Percentage of Participants With HRS Reversal
Outcome Description
Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30
Outcome Time Frame
Day 30
Outcome Measure
Percentage of Participants With Durable HRS Reversal
Outcome Description
Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge
Outcome Time Frame
within 14 days
Outcome Measure
Percentage pf Participants in the SIRS Subgroup With HRS Reversal
Outcome Description
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
Outcome Time Frame
Day 30
Outcome Measure
Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240