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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Portal Hypertension, Liver Cirrhosis

Intervention / Treatment
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* Drug: Ifetroban
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ifetroban<br>90 day course of oral ifetroban following intravenous loading dose | Drug: Ifetroban<br>* thromboxane prostanoid receptor antagonist delivered as infusion and oral capsule<br>|
| Placebo Comparator: Placebo<br>90 day course of placebo following intravenous dose of 5% dextrose in water (D5W) | Drug: Placebo<br>* matched placebo delivered as infusion and oral capsule<br>|

What is the study measuring?
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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 |