Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients
A Multi-Center, Double-Blind, Randomized, Controlled Study to Determine the Safety and Pharmacokinetics of Ifetroban Injection in Hepatorenal Syndrome
1 other identifier
interventional
55
2 countries
12
Brief Summary
A study of ifetroban in the treatment of hepatorenal syndrome (HRS) in hospitalized adult patients to assess the safety and pharmacokinetics of 3 days of intravenous ifetroban.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2011
Typical duration for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 31, 2011
CompletedFirst Posted
Study publicly available on registry
September 19, 2011
CompletedStudy Start
First participant enrolled
October 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2015
CompletedResults Posted
Study results publicly available
February 14, 2017
CompletedMarch 1, 2017
February 1, 2017
3.7 years
August 31, 2011
December 22, 2016
February 27, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide
Plasma concentrations of ifetroban and its major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
3 days
Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
Plasma concentrations of ifetroban and its primary active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
3 days
Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
Plasma concentrations of ifetroban and it's major active metabolite were measured at Baseline and Study Hours 1, 2, 4, 8, 12, 24, 48, 49, 50, 52, 56, 60, and 72 to determine the Pharmacokinetic parameters.
3 days
Secondary Outcomes (4)
Safety: Day 28 Mortality
28 days
Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL
Day 0 through Day 5
The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements
Day 0 to Day 5
Change in 24-hour Urine Volume
Baseline to Hour 96
Study Arms (9)
5 mg ifetroban, Type 1
EXPERIMENTAL60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
Placebo, Type 1
PLACEBO COMPARATOR60-minute intravenous infusion of 5% dextrose in sterile water given once daily for 3 days to subjects with Type 1 HRS.
5 mg ifetroban, Type 2
EXPERIMENTAL60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
15 mg ifetroban, Type 1
EXPERIMENTAL60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
15 mg ifetroban, Type 2
EXPERIMENTAL60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.
50 mg ifetroban, Type 1
EXPERIMENTAL60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.
50 mg ifetroban, Type 2
EXPERIMENTAL60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.
150 mg ifetroban, Type 2
EXPERIMENTAL60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.
Placebo, Type 2
PLACEBO COMPARATOR60-minute intravenous infusion of 5% dextrose in sterile water given once daily for 3 days to subjects with Type 2 HRS.
Interventions
Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Eligibility Criteria
You may qualify if:
- Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary).
- Subjects with either Type 1 or Type 2 HRS defined in a and b below:
- a. Type 1: i. At least a doubling of the serum creatinine to a minimum of 220 µmol/L (2.5 mg/dL) at enrollment, occurring over a period of less than 14 days, OR ii. A 50% or greater reduction in the estimated glomerular filtration rate (GFR - calculated by the method of Cockcroft-Gault) to below 20 mL/min at enrollment occurring over a period of less than 14 days.
- iii. A projected doubling of serum creatinine to a minimum of 2.5 mg/dL, expected to occur in less than 14 days based on the rate of change observed.
- b. Type 2: defined as at least a 33% reduction in creatinine clearance occurring over a period of greater than 2 weeks, with a serum creatinine (SCr) \> 133µmol/L (1.5 mg/dL).
- Oliguria occurring within 48 hours prior to the first administration CTM. Oliguria is defined as an average urine output of \< 35 mL/hr (measured for a minimum of 4 hours) under either of the following circumstances:
- a. When measured central venous pressure (CVP) \> 12 mmHg, OR b. following a fluid challenge consisting of either: i. at minimum 20 mL/kg isotonic fluid (e.g. any combination of 5% albumin, normal saline, blood or blood products) given over no more than 6 hours ii. at minimum 1 g/kg of hypertonic fluid (e.g. 25% albumin) given over no more than 24 hours iii. an equivalent combination of 3.b.i and 3.b.ii
You may not qualify if:
- History of allergy or hypersensitivity to ifetroban
- Pregnant or nursing
- Less than 18 years of age
- Serum creatinine at the time of enrollment greater than or equal to 5.0 mg/dL
- Platelet count at screening less than 30 x 10\^3 platelets/µL
- Anticipated of planned need for dialysis within 5 days of first CTM dose.
- Active gastrointestinal hemorrhage (where active is defined as evidence of bleeding within 48 hours of the first dose of CTM)
- Evidence of current (within past 30 days) obstructive (post-renal) or intrinsic renal disease \[including but not limited to: acute tubular necrosis (ATN), glomerular diseases/glomerulonephritis, acute interstitial nephritis (AIN), known urinary obstruction, proteinuria \> 500 mg/day, microhematuria (\> 50 RBCs/high power field), abnormal renal ultrasound, fractional excretion of sodium (FeNa) \> 2.0%, any urinary casts other than hyaline.
- Current or recent (within the preceding 5 days) treatment with nephrotoxic drugs including but not limited to: NSAIDs (prior 48 hours), angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), calcineurin inhibitors (cyclosporine, tacrolimus), aminoglycosides, amphotericin B, antiretrovirals and antivirals (adefovir, cidofovir, tenofovir, acyclovir, indinavir), cisplatin, methotrexate, cyclosporine, amphotericin B contrast agents, foscarnet, zoledronate, etc.
- Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG.
- New York Heart Association class 3 or 4 heart failure.
- Presence of hepatocellular carcinoma not transplantable by Milan criteria
- Cardiopulmonary arrest without full recovery of mental status
- Moribund and death expected within five days
- Bacterial or fungal infections which have been unresponsive to at least 24 hours of appropriate antimicrobial therapy
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Mayo Clinic - Arizona
Phoenix, Arizona, 85054, United States
UCSD, Hillcrest Medical Center Hospital
La Jolla, California, 92093, United States
UCSF (University of California-San Francisco)
San Francisco, California, 94143, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
Indiana University (Division of Gastroenterology/Hepatology)
Indianapolis, Indiana, 46202, United States
University of Michigan Hospital
Ann Arbor, Michigan, 48109, United States
NYU Langone Medical Center
New York, New York, 10016, United States
The Ohio State University
Columbus, Ohio, 43210, United States
Baylor All Saints Medical Center
Fort Worth, Texas, 76104, United States
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
MIDAS Multispeciality Hospital PVT LTD
Nagpur, Maharashtra, 440010, India
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jerry Fox, DVM
- Organization
- Cumberland Pharmaceuticals Inc
Study Officials
- PRINCIPAL INVESTIGATOR
Brendan McGuire, MD
University of Alabama at Birmingham
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 31, 2011
First Posted
September 19, 2011
Study Start
October 1, 2011
Primary Completion
June 1, 2015
Study Completion
July 1, 2015
Last Updated
March 1, 2017
Results First Posted
February 14, 2017
Record last verified: 2017-02
Data Sharing
- IPD Sharing
- Will not share