Study To Confirm Efficacy and Safety of Terlipressin in Hepatorenal Syndrome (HRS) Type 1
- Registration Number
- NCT02770716
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 300
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Terlipressin 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. Placebo 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Verified HRS Reversal 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.
Percentage of Participants Who Were Viable (Per Protocol) for Inclusion in the Primary End Point Analysis 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
Name Time Method Percentage of Participants With Verified HRS Reversal Without HRS Recurrence by Day 30 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
Percentage pf Participants in the SIRS Subgroup With HRS Reversal within 14 days Defined as the percentage of participants in the SIRS subgroup with HRS reversal by Day 14 or discharge
Percentage of Participants With HRS Reversal 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
Percentage of Participants With Durable HRS Reversal Day 30 Defined as the percentage of participants maintaining HRS reversal without RRT to Day 30
Trial Locations
- Locations (64)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Banner Good Samaritan Medical Center
🇺🇸Phoenix, Arizona, United States
Mayo Clinic - AZ
🇺🇸Phoenix, Arizona, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
USC Healthcare
🇺🇸Los Angeles, California, United States
Stanford Hospital and Clinics
🇺🇸Palo Alto, California, United States
UCLA Medical Center
🇺🇸San Diego, California, United States
Southern California Research Center
🇺🇸San Diego, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
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