Study to Assess Safety and Efficacy of Ifetroban for Treatment of Portal Hypertension in Cirrhotic Patients
Primary Purpose
Portal Hypertension, Liver Cirrhosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ifetroban
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Portal Hypertension
Eligibility Criteria
Inclusion Criteria:
- liver cirrhosis
- baseline hepatic venous pressure gradient (HVPG) >= 8 mmHg and <= 18 mmHg
- stable liver function enzymes
Exclusion Criteria:
- portal or splenic vein thrombosis
- Transjugular intrahepatic portosystemic shunt (TIPS) or portocaval shunt
- variceal bleed in last 2 months
- hemodialysis
- Child-Pugh Score >= 12
- Model for End-stage Liver Disease- Sodium score (MELD-Na) >= 20
- Acute kidney injury, Chronic kidney disease and/or Serum Creatinine >= 2.0 mg/dL
- current alcohol consumption > 2 drinks per day
- Platelet count (PLT) < 60 x 10^3/microliter (uL)
- A change in statin therapy in the last 3 months
- Current Hepatitis Virus B or C (HBV or HCV) therapy; or planned initiation of therapy during the treatment period
- Myocardial infarction within 30 days
- History of bleeding diathesis or current (within previous 14 days) or planned use of anticoagulant or antiplatelet drugs including aspirin
Sites / Locations
- Tampa General Medical Group
- Indiana University
- The Ohio State University Wexner Medical Center
- Medical University of South Carolina
- Baylor University Medical Center
- Virginia Commonwealth University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ifetroban
Placebo
Arm Description
90 day course of oral ifetroban following intravenous loading dose
90 day course of placebo following intravenous dose of 5% dextrose in water (D5W)
Outcomes
Primary Outcome Measures
Safety (Incidence and Severity of Adverse Events)
Incidence is measured as the total number of adverse events reported during the treatment and follow-up period for each treatment group.
Safety (Severity of Adverse Events)
The severity of each event is reported by the investigator according to the following protocol/CTCAE definitions: Grade 1-Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2-Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3-Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4-Life-threatening consequences; urgent intervention indicated; Grade 5-Death related to adverse event.
Secondary Outcome Measures
Change in Hepatic Venous Pressure Gradient (HVPG)
The HVPG will be measured through Day 90 and will be compared to baseline
Change in Aspartate Aminotransferase (AST)
AST values through Day 90 will be compared to baseline
Alanine Aminotransferase (ALT)
ALT values through Day 90 will be compared to baseline
Aspartate Aminotransferase/Platelet Ratio (APRI)
The Aspartate Aminotransferase/Platelet Ratio through Day 90 will be compared to baseline
Variceal Bleeds (Occurrence of Variceal Bleeds)
The number of variceal bleeds during the treatment and follow-up periods will be evaluated
Full Information
NCT ID
NCT02802228
First Posted
June 9, 2016
Last Updated
January 17, 2022
Sponsor
Cumberland Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02802228
Brief Title
Study to Assess Safety and Efficacy of Ifetroban for Treatment of Portal Hypertension in Cirrhotic Patients
Official Title
A Randomized, Double-blind, Placebo-controlled Pilot Study to Assess the Safety and Efficacy of Ifetroban for the Treatment of Portal Hypertension in Cirrhotic Patients
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
March 6, 2017 (Actual)
Primary Completion Date
July 17, 2018 (Actual)
Study Completion Date
July 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cumberland Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This placebo-controlled study will assess the safety and efficacy of a 90-day course of treatment with ifetroban for portal hypertension in cirrhotic patients
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Portal Hypertension, Liver Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ifetroban
Arm Type
Experimental
Arm Description
90 day course of oral ifetroban following intravenous loading dose
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
90 day course of placebo following intravenous dose of 5% dextrose in water (D5W)
Intervention Type
Drug
Intervention Name(s)
Ifetroban
Intervention Description
thromboxane prostanoid receptor antagonist delivered as infusion and oral capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matched placebo delivered as infusion and oral capsule
Primary Outcome Measure Information:
Title
Safety (Incidence and Severity of Adverse Events)
Description
Incidence is measured as the total number of adverse events reported during the treatment and follow-up period for each treatment group.
Time Frame
Through 97 days (90 days treatment and 7 days follow-up)
Title
Safety (Severity of Adverse Events)
Description
The severity of each event is reported by the investigator according to the following protocol/CTCAE definitions: Grade 1-Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2-Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living; Grade 3-Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4-Life-threatening consequences; urgent intervention indicated; Grade 5-Death related to adverse event.
Time Frame
Through 90 days treatment and 7 days follow-up
Secondary Outcome Measure Information:
Title
Change in Hepatic Venous Pressure Gradient (HVPG)
Description
The HVPG will be measured through Day 90 and will be compared to baseline
Time Frame
Baseline and 90 days
Title
Change in Aspartate Aminotransferase (AST)
Description
AST values through Day 90 will be compared to baseline
Time Frame
Baseline and 90 days
Title
Alanine Aminotransferase (ALT)
Description
ALT values through Day 90 will be compared to baseline
Time Frame
Baseline and 90 days
Title
Aspartate Aminotransferase/Platelet Ratio (APRI)
Description
The Aspartate Aminotransferase/Platelet Ratio through Day 90 will be compared to baseline
Time Frame
Baseline and 90 days
Title
Variceal Bleeds (Occurrence of Variceal Bleeds)
Description
The number of variceal bleeds during the treatment and follow-up periods will be evaluated
Time Frame
Through Day 97
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
liver cirrhosis
baseline hepatic venous pressure gradient (HVPG) >= 8 mmHg and <= 18 mmHg
stable liver function enzymes
Exclusion Criteria:
portal or splenic vein thrombosis
Transjugular intrahepatic portosystemic shunt (TIPS) or portocaval shunt
variceal bleed in last 2 months
hemodialysis
Child-Pugh Score >= 12
Model for End-stage Liver Disease- Sodium score (MELD-Na) >= 20
Acute kidney injury, Chronic kidney disease and/or Serum Creatinine >= 2.0 mg/dL
current alcohol consumption > 2 drinks per day
Platelet count (PLT) < 60 x 10^3/microliter (uL)
A change in statin therapy in the last 3 months
Current Hepatitis Virus B or C (HBV or HCV) therapy; or planned initiation of therapy during the treatment period
Myocardial infarction within 30 days
History of bleeding diathesis or current (within previous 14 days) or planned use of anticoagulant or antiplatelet drugs including aspirin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Don Rockey, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tampa General Medical Group
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Virginia Commonwealth University Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Assess Safety and Efficacy of Ifetroban for Treatment of Portal Hypertension in Cirrhotic Patients
We'll reach out to this number within 24 hrs