Safety and Pharmacokinetics of Ifetroban in Hepatorenal Syndrome Patients

• Sponsor: Cumberland Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01436500
• Collaborator: (none)
• Enrollment: 55
• Locations: 12
• Arms: 9
• Duration (Months): 45
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatorenal Syndrome	Drug: Ifetroban Injection; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Double-Blind, Randomized, Controlled Study to Determine the Safety and Pharmacokinetics of Ifetroban Injection in Hepatorenal Syndrome
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Placebo Comparator: 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.	Drug: Placebo; Sterile water with 5% Dextrose; Other Names: D5W
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Experimental: 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.	Drug: Ifetroban Injection; Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Placebo Comparator: 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.	Drug: Placebo; Sterile water with 5% Dextrose; Other Names: D5W

Outcome Measures

Primary Outcome Measures

1. Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide [3 days]

   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.

2. Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment [3 days]

   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. Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment [3 days]

   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.

Secondary Outcome Measures

1. Safety: Day 28 Mortality [28 days]

2. Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL [Day 0 through Day 5]

3. The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements [Day 0 to Day 5]

4. Change in 24-hour Urine Volume [Baseline to Hour 96]

   The volume of urine collected in a 24-hour post-treatment period minus the volume collected in a 24-hour pre-treatment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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.

1. 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.

1. 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).

1. 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:

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic - Arizona	Phoenix	Arizona	United States	85054
2	UCSD, Hillcrest Medical Center Hospital	La Jolla	California	United States	92093
3	UCSF (University of California-San Francisco)	San Francisco	California	United States	94143
4	Emory University Hospital	Atlanta	Georgia	United States	30322
5	Indiana University (Division of Gastroenterology/Hepatology)	Indianapolis	Indiana	United States	46202
6	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109
7	NYU Langone Medical Center	New York	New York	United States	10016
8	The Ohio State University	Columbus	Ohio	United States	43210
9	Baylor All Saints Medical Center	Fort Worth	Texas	United States	76104
10	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
11	Virginia Commonwealth University	Richmond	Virginia	United States	23298
12	MIDAS Multispeciality Hospital PVT LTD	Nagpur	Maharashtra	India	440010

Sponsors and Collaborators

• Cumberland Pharmaceuticals

Investigators

• Principal Investigator: Brendan McGuire, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cumberland Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01436500
• Other Study ID Numbers: CPI-IFE-001
• First Posted: Sep 19, 2011
• Last Update Posted: Mar 1, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Cumberland Pharmaceuticals: Hepatorenal Syndrome; HRS; ifetroban
• Additional relevant MeSH terms: Hepatorenal Syndrome; Syndrome; Ifetroban

Study Results

Participant Flow

Arm/Group Title	5 mg Ifetroban	15 mg Ifetroban	50 mg Ifetroban	150 mg Ifetroban	Placebo
Arm/Group Description	5 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	15 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	50 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Period Title: Overall Study
STARTED	12	12	12	6	13
COMPLETED	9	9	7	5	9
NOT COMPLETED	3	3	5	1	4

Baseline Characteristics

Arm/Group Title	Ifetroban Injection	Placebo	Total
Arm/Group Description	5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	5% Dextrose in Water administered IV over 60 minutes once daily x 3 days	Total of all reporting groups
Overall Participants	42	13	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57 (9.7)	56 (6.4)	57 (9.0)
Sex: Female, Male (Count of Participants)
Female	17 40.5%	5 38.5%	22 40%
Male	25 59.5%	8 61.5%	33 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 19%	6 46.2%	14 25.5%
Not Hispanic or Latino	34 81%	7 53.8%	41 74.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.4%	0 0%	1 1.8%
Asian	3 7.1%	1 7.7%	4 7.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 2.4%	0 0%	1 1.8%
White	37 88.1%	12 92.3%	49 89.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Half-life (T-1/2) of Ifetroban and Ifetroban Acylglucuronide
Description	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.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

Patients from which a full series of plasma samples were obtained from baseline through Hour 72 were included in the calculations of the PK parameters. Where the number of participants analyzed in an arm is lower than the number exposed for that arm, the patients with missing data did not contribute to the calculation of the PK parameters.

Arm/Group Title	5 mg Ifetroban, Type 1	5 mg Ifetroban, Type 2	15 mg Ifetroban, Type 1	15 mg Ifetroban, Type 2	50 mg Ifetroban, Type 1	50 mg Ifetroban, Type 2	150 mg Ifetroban, Type 2
Arm/Group Description	60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Measure Participants	5	5	5	5	3	5	3
half-life ifetroban	36.0 (NA)	11.9 (18.4)	15.7 (16.7)	10.5 (8.6)	18.1 (14.8)	13.5 (8.2)	17.4 (11.7)
half-life ifetroban acylglucuronide	17.1 (17.5)	14.7 (19.9)	22.1 (9.5)	18.6 (10.9)	26.4 (22.0)	15.2 (9.5)	12.6 (12.4)

2. Primary Outcome

Title	Pharmacokinetic Parameters (Exposure) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
Description	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.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

Patients from which a full series of plasma samples were obtained from baseline through Hour 72 were included in the calculations of the PK parameters. Where the number of participants analyzed in an arm is lower than the number exposed for that arm, the patients with missing data did not contribute to the calculation of the PK parameters.

Arm/Group Title	5 mg Ifetroban, Type 1	5 mg Ifetroban, Type 2	15 mg Ifetroban, Type 1	15 mg Ifetroban, Type 2	50 mg Ifetroban, Type 1	50 mg Ifetroban, Type 2	150 mg Ifetroban, Type 2
Arm/Group Description	60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Measure Participants	5	5	5	5	3	5	3
Ifetroban area under the curve (AUC) to 24 hours	964 (683)	779 (326)	2025 (639)	2463 (1497)	5151 (3579)	6634 (2166)	18612 (8408)
Ifetroban AUC to infinity	2476 (NA)	906 (481)	2959 (1941)	3259 (2866)	6505 (4032)	8204 (3461)	24657 (13425)
Ifetroban acylglucuronide AUC to 24 hours to	4371 (2050)	4145 (781)	12192 (2102)	12038 (2734)	46455 (2906)	42051 (18567)	109915 (32895)
Ifetroban acylglucuronide AUC to infinity	8440 (8730)	6128 (3721)	21962 (7404)	29857 (27688)	86457 (44928)	61673 (25672)	144951 (61311)

3. Primary Outcome

Title	Pharmacokinetic Parameters (Concentration) of Ifetroban and Ifetroban Acylglucuronide After Three Days of Treatment
Description	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.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

Patients from which a full series of plasma samples were obtained from baseline through Hour 72 were included in the calculations of the PK parameters. Where the number of participants analyzed in an arm is lower than the number exposed for that arm, the patients with missing data did not contribute to the calculation of the PK parameters.

Arm/Group Title	5 mg Ifetroban, Type 1	5 mg Ifetroban, Type 2	15 mg Ifetroban, Type 1	15 mg Ifetroban, Type 2	50 mg Ifetroban, Type 1	50 mg Ifetroban, Type 2	150 mg Ifetroban, Type 2
Arm/Group Description	60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 5 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 15 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 1 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 50 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose	60-minute intravenous infusion of 150 mg ifetroban given once daily for 3 days to subjects with Type 2 HRS. Ifetroban Injection: Ifetroban sodium injectable, diluted in sterile water with 5% dextrose
Measure Participants	5	5	5	5	3	5	3
Minimum Concentration Ifetroban	1.8 (4.1)	3.4 (4.0)	14.1 (22.6)	23.5 (33.7)	43.3 (36.2)	51.1 (44.5)	150.0 (115.5)
Maximum Concentration Ifetroban	483 (445)	251 (107)	581 (114)	785 (225)	1666 (1478)	2599 (838)	6790 (2777)
Minimum Concentration Ifetroban Acylglucuronide	78.4 (56.7)	41.4 (33.1)	241.9 (89.0)	200.2 (114.3)	778.0 (583.2)	632.9 (302.9)	1755.0 (792.4)
Maximum Concentration Ifetroban Acylglucuronide	384 (103)	448 (101)	912 (194)	1214 (255)	4737 (543)	4666 (1748)	10447 (2113)

4. Secondary Outcome

Title	Safety: Day 28 Mortality
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ifetroban Injection	Placebo
Arm/Group Description	5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Measure Participants	42	13
Number [percentage of participants]	17 40.5%	15 115.4%

5. Secondary Outcome

Title	Percentage of Patients Achieving a Treatment-period Serum Creatinine Reduction Below 1.5 mg/dL
Time Frame	Day 0 through Day 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ifetroban Injection	Placebo
Arm/Group Description	5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Measure Participants	42	13
Number [percentage of participants]	21 50%	15 115.4%

6. Secondary Outcome

Title	The Percentage of Patients Achieving a Reduction of Creatinine Clearance to Below Baseline on Two Consecutive Daily Measurements
Time Frame	Day 0 to Day 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ifetroban Injection	Placebo
Arm/Group Description	5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Measure Participants	42	13
Number [percentage of participants]	62 147.6%	77 592.3%

7. Secondary Outcome

Title	Change in 24-hour Urine Volume
Description	The volume of urine collected in a 24-hour post-treatment period minus the volume collected in a 24-hour pre-treatment period.
Time Frame	Baseline to Hour 96

Outcome Measure Data

Analysis Population Description

Data were missing for the post-treatment urine volume measurements in 9 of 42 ifetroban patients and 3 of 13 placebo patients so they were excluded from the analysis.

Arm/Group Title	Ifetroban Injection	Placebo
Arm/Group Description	5, 15, 50, or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days	5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
Measure Participants	33	10
Mean (Standard Deviation) [mL]	267.3 (613.3)	-118.5 (452.2)

Adverse Events

Time Frame	Day 0 through Day 28
Adverse Event Reporting Description	A secondary objective of the study was to evaluate the tolerability and safety of ifetroban in HRS patients. All ifetroban patients are grouped together for comparison to all placebo patients for the purpose of maximizing the significance of the evaluation.
Arm/Group Title	Ifetroban		Placebo
Arm/Group Description	5, 15, 50 or 150 mg Ifetroban Injection administered IV over 60 minutes once daily x 3 days		5% Dextrose in Water administered IV over 60 minutes once daily x 3 days
All Cause Mortality
	Ifetroban		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/42 (16.7%)		2/13 (15.4%)
Serious Adverse Events
	Ifetroban		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/42 (50%)		8/13 (61.5%)
Cardiac disorders
Atrial fibrillation	1/42 (2.4%)		0/13 (0%)
Endocrine disorders
hyperglycaemia	0/42 (0%)		1/13 (7.7%)
Gastrointestinal disorders
worsening ascites	0/42 (0%)		1/13 (7.7%)
haematemesis	1/42 (2.4%)		0/13 (0%)
haematochezia	1/42 (2.4%)		0/13 (0%)
peritoneal haemorrhage	2/42 (4.8%)		0/13 (0%)
General disorders
catheter site haemorrhage	1/42 (2.4%)		0/13 (0%)
device failure	1/42 (2.4%)		0/13 (0%)
Hepatobiliary disorders
chronic hepatic failure	3/42 (7.1%)		0/13 (0%)
hepatic cirrhosis	0/42 (0%)		1/13 (7.7%)
hepatorenal syndrome	1/42 (2.4%)		1/13 (7.7%)
liver disorder	1/42 (2.4%)		0/13 (0%)
Infections and infestations
bacteraemia	1/42 (2.4%)		0/13 (0%)
peritonitis bacterial	1/42 (2.4%)		0/13 (0%)
pneumonia	0/42 (0%)		1/13 (7.7%)
Injury, poisoning and procedural complications
complications of transplanted liver	1/42 (2.4%)		0/13 (0%)
post procedural haematoma	1/42 (2.4%)		0/13 (0%)
Investigations
Blood Creatinine Increased	0/42 (0%)		1/13 (7.7%)
Psychiatric disorders
mental status changes	0/42 (0%)		1/13 (7.7%)
Renal and urinary disorders
renal failure	1/42 (2.4%)		0/13 (0%)
Renal failure chronic	1/42 (2.4%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
hypoxia	1/42 (2.4%)		0/13 (0%)
respiratory failure	1/42 (2.4%)		0/13 (0%)
Vascular disorders
deep vein thrombosis	1/42 (2.4%)		0/13 (0%)
shock haemorrhagic	1/42 (2.4%)		0/13 (0%)
subarachnoid haemorrhage	0/42 (0%)		1/13 (7.7%)
upper gastrointestinal haemorrhage	1/42 (2.4%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Ifetroban		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/42 (59.5%)		5/13 (38.5%)
Blood and lymphatic system disorders
anaemia	3/42 (7.1%)		0/13 (0%)
worsening coagulopathy	0/42 (0%)		1/13 (7.7%)
Cardiac disorders
Dyspnoea	5/42 (11.9%)		0/13 (0%)
atrial fibrillation	3/42 (7.1%)		0/13 (0%)
Bradycardia	1/42 (2.4%)		1/13 (7.7%)
Gastrointestinal disorders
abdominal pain	4/42 (9.5%)		0/13 (0%)
nausea	3/42 (7.1%)		0/13 (0%)
Hepatobiliary disorders
chronic hepatic failure	3/42 (7.1%)		0/13 (0%)
Investigations
INR increased	0/42 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
hyperkalaemia	1/42 (2.4%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
pain in extremity	0/42 (0%)		1/13 (7.7%)
Renal and urinary disorders
worsening renal function	1/42 (2.4%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
dyspnoea	2/42 (4.8%)		1/13 (7.7%)
respiratory failure	0/42 (0%)		1/13 (7.7%)
Vascular disorders
hypotension	3/42 (7.1%)		1/13 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI can publish data generated at their study site after multi=center study data have already been published, or after 18 months have elapsed following database lock. The sponsor may review manuscripts before submission and delay publication by an additional 60 days, if necessary.