Study to Assess Safety and Efficacy of Ifetroban for Treatment of Portal Hypertension in Cirrhotic Patients

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

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

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Portal Hypertension
• Intervention / Treatment: Drug: Ifetroban; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23114
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ifetroban; 90 day course of oral ifetroban following intravenous loading dose	Drug: Ifetroban; thromboxane prostanoid receptor antagonist delivered as infusion and oral capsule
PLACEBO_COMPARATOR: Placebo; 90 day course of placebo following intravenous dose of 5% dextrose in water (D5W)	Drug: Placebo; matched placebo delivered as infusion and oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Through 97 days (90 days treatment and 7 days follow-up)
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.	Through 90 days treatment and 7 days follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hepatic Venous Pressure Gradient (HVPG)	The HVPG will be measured through Day 90 and will be compared to baseline	Baseline and 90 days
Change in Aspartate Aminotransferase (AST)	AST values through Day 90 will be compared to baseline	Baseline and 90 days
Alanine Aminotransferase (ALT)	ALT values through Day 90 will be compared to baseline	Baseline and 90 days
Aspartate Aminotransferase/Platelet Ratio (APRI)	The Aspartate Aminotransferase/Platelet Ratio through Day 90 will be compared to baseline	Baseline and 90 days
Variceal Bleeds (Occurrence of Variceal Bleeds)	The number of variceal bleeds during the treatment and follow-up periods will be evaluated	Through Day 97

Collaborators and Investigators

• Sponsor: Cumberland Pharmaceuticals
• Investigators: Principal Investigator: Don Rockey, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 6, 2017
• Primary Completion (ACTUAL): July 17, 2018
• Study Completion (ACTUAL): July 17, 2018

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 13, 2016
• First Posted (ESTIMATE): June 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 17, 2022
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Fibrosis; Hypertension; Liver Cirrhosis; Hypertension, Portal; Platelet Aggregation Inhibitors; Ifetroban
• Other Study ID Numbers: CPI-IFE-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No