Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients

NCT ID: NCT01436500

Last Updated: 2017-03-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

55 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2015-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Hepatorenal Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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5 mg ifetroban, Type 1

60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

Placebo, Type 1

60-minute intravenous infusion of 5% dextrose in sterile water given once daily for 3 days to subjects with Type 1 HRS.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Sterile water with 5% Dextrose

5 mg ifetroban, Type 2

60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

15 mg ifetroban, Type 1

60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

15 mg ifetroban, Type 2

60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

50 mg ifetroban, Type 1

60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

50 mg ifetroban, Type 2

60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

150 mg ifetroban, Type 2

60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS.

Group Type EXPERIMENTAL

Ifetroban Injection

Intervention Type DRUG

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

Placebo, Type 2

60-minute intravenous infusion of 5% dextrose in sterile water given once daily for 3 days to subjects with Type 2 HRS.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Sterile water with 5% Dextrose

Interventions

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Ifetroban Injection

Ifetroban sodium injectable, diluted in sterile water with 5% dextrose

Intervention Type DRUG

Placebo

Sterile water with 5% Dextrose

Intervention Type DRUG

Other Intervention Names

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D5W

Eligibility Criteria

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Inclusion Criteria

1. Chronic liver disease, defined as cirrhosis with ascites based on clinical findings (biopsy not necessary).
2. 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).
3. 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

Exclusion Criteria

1. History of allergy or hypersensitivity to ifetroban
2. Pregnant or nursing
3. Less than 18 years of age
4. Serum creatinine at the time of enrollment greater than or equal to 5.0 mg/dL
5. Platelet count at screening less than 30 x 10\^3 platelets/µL
6. Anticipated of planned need for dialysis within 5 days of first CTM dose.
7. Active gastrointestinal hemorrhage (where active is defined as evidence of bleeding within 48 hours of the first dose of CTM)
8. 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.
9. 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.
10. Presence of shock defined as hypotension, with a mean arterial pressure less than 50 mmHG.
11. New York Heart Association class 3 or 4 heart failure.
12. Presence of hepatocellular carcinoma not transplantable by Milan criteria
13. Cardiopulmonary arrest without full recovery of mental status
14. Moribund and death expected within five days
15. Bacterial or fungal infections which have been unresponsive to at least 24 hours of appropriate antimicrobial therapy
16. Burns \> 30% body surface area
17. Exposed to investigational drugs within 30 days before 1st CTM administration.
18. Inability to understand the requirements of the study. (Subjects must be willing to provide written informed consent or consent of legally recognized representative, as evidenced by signature on an informed consent document approved by an Institutional Review Board \[IRB\], and agree to abide by the study restrictions. If the subject is incapacitated, informed consent will be sought from a legally recognized representative).
19. Refusal to provide written authorization for use and disclosure of protected health information.
20. Be otherwise unsuitable for the study, in the opinion of the Investigator.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cumberland Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Brendan McGuire, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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Mayo Clinic - Arizona

Phoenix, Arizona, United States

Site Status

UCSD, Hillcrest Medical Center Hospital

La Jolla, California, United States

Site Status

UCSF (University of California-San Francisco)

San Francisco, California, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

Indiana University (Division of Gastroenterology/Hepatology)

Indianapolis, Indiana, United States

Site Status

University of Michigan Hospital

Ann Arbor, Michigan, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Baylor All Saints Medical Center

Fort Worth, Texas, United States

Site Status

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

MIDAS Multispeciality Hospital PVT LTD

Nagpur, Maharashtra, India

Site Status

Countries

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United States India

Other Identifiers

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CPI-IFE-001

Identifier Type: -

Identifier Source: org_study_id

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