Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

Study Overview
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Brief Summary
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The overall aim of the study is to determine the efficacy of oral ifetroban, a novel antagonist of T prostanoid (TP) receptors, as a treatment for patients with aspirin-exacerbated respiratory disease (AERD).

Detailed Description
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The protocol involves a 4-week, double-blind, placebo-controlled parallel-design trial of oral ifetroban in patients with AERD. At the end of the 4-week treatment phase (ifetroban or placebo) each subject will undergo a graded oral aspirin desensitization procedure in order to initiate high-dose aspirin therapy, which is standard-of-care at our institution and is the only available therapy known to modify the course of AERD.

Official Title
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Therapeutic Control of Aspirin-Exacerbated Respiratory Disease

Conditions
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Nasal Polyps, Asthma, Aspirin-Induced, Aspirin-exacerbated Respiratory Disease, Aspirin-Sensitive Asthma With Nasal Polyps

Intervention / Treatment
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* Drug: Ifetroban
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of AERD, defined as meeting the diagnostic triad with: History of physician-diagnosed asthma and History of physician-diagnosed nasal polyposis and History of pathognomonic reactions aspirin or other nonselective cyclooxygenase (COX) inhibitors. Stable asthma (post-bronchodilator forced expiratory volume at one second (FEV1) of ≥70%, no glucocorticoid burst for at least 2 weeks prior to Visit 1, and no hospitalizations or ER visits for asthma for at least the prior 6 months) Age between 18 and 70 years No current smoking (not more than one instance of smoking in the last 3 months) Non-pregnant Exclusion Criteria: Hypersensitivity to montelukast Current use of zileuton History of bleeding diathesis or use of anticoagulant or antiplatelet drugs Current use of any NSAIDs aside from the aspirin provided during the study Current use of beta blockers Use of any biologics within the last 4 months prior to initiating the study

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ifetroban<br>Subjects will be randomized to receive ifetroban (200 mg dose per day) for 4 weeks. | Drug: Ifetroban<br>* 4-week, double-blind, placebo-controlled parallel-design trial of oral ifetroban (a TP receptor antagonist) in patients with AERD<br>* Other names: ifetroban sodium;|
| Placebo Comparator: Placebo<br>Subjects will be randomized to receive placebo for 4 weeks. | Drug: Placebo<br>* 4-week, double-blind, placebo-controlled parallel-design trial of oral ifetroban (a TP receptor antagonist) in patients with AERD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Provocative Dose 2 (PD2) During Aspirin Challenge | The calculated dose of aspirin that induces an increase in the Total Nasal Symptom Score (TNSS) of 2 from the pre-aspirin challenge value, PD2 TNSS: A higher TNSS score suggests more severe symptoms, on a scale from 0-65 PD2: A higher PD2 suggests that the patient's threshold of reactivity of aspirin was higher | 6 weeks from screening visit ( at visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline of FEV1 During Aspirin Challenge (Bronchoconstriction) | Severity of bronchoconstriction during the aspirin-induced reaction at Visit 2, compared between patients on placebo vs ifetroban, with the changes also analyzed with provocative aspirin dose as a covariate. Measured by an aspirin-induced decrease in FEV1. | At Visit 2. The change in FEV1 from the morning baseline to the aspirin-induced lowest value in FEV1 during reaction to aspirin challenge later that same day. | 
| Aspirin-induced Leukotriene E4 (LTE4) Levels | Increase of urinary levels of LTE4 during aspirin-induced reaction from Visit 2 pre-aspirin levels, compared between patients on placebo vs ifetroban, with the changes also analyzed with provocative aspirin dose as a covariate. LTE4 levels were calculated in a specialized laboratory. | Visit 2. The change in LTE4 levels from the morning baseline to the aspirin-induced highest value in LTE4 during reaction to aspirin challenge that same day. | 
| Change in Chronic Disease Control by Measurement of Lung Function Through FEV1 | Change from Visit 1 in baseline FEV1,compared between patients on placebo vs ifetroban. | 1 month (between Visit 1 and Visit 2) | 
| Change in Chronic Disease by Measurement of Asthma Control Through Asthma Control Questionnaire (ACQ) Score | Change from Visit 1 in baseline ACQ (Asthma Control Questionnaire) score, compared between patients on placebo vs ifetroban. ACQ is a patient-reported questionnaire measurement of asthma control from 0-6, where lower scores suggest better asthma control. The score is the average result of the answer choices picked by the patient. | 1 month (between Visit 1 and Visit 2) | 
| Clinical Improvement of Chronic Disease - Sino-Nasal Outcome Test (SNOT-22) Score | Change from Visit 1 in baseline SNOT-22 score at Visit 2, compared between patients on placebo vs ifetroban. The SNOT-22 is a patient-reported questionnaire with a summed scale that goes from 0-110 and a lower score suggests better sinonasal control. | 1 month (between Visit 1 and Visit 2) | 
| Fractional Exhaled Nitric Oxide (FeNO) | Change from Visit 1 in baseline FeNO levels at Visit 2, compared between patients on placebo vs ifetroban. | 1 month (between Visit 1 and Visit 2) |