Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

Phase 2

Completed

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

Interventions: Drug: Placebo
Drug: Ifetroban

Registration Number: NCT03326063

Lead Sponsor: Brigham and Women's Hospital

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will be randomized to receive placebo for 4 weeks.
Ifetroban	Ifetroban	Subjects will be randomized to receive ifetroban (200 mg dose per day) for 4 weeks.

Primary Outcome Measures

Name	Time	Method
Provocative Dose 2 (PD2) During Aspirin Challenge	6 weeks from screening visit ( at visit 2)	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

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline of FEV1 During Aspirin Challenge (Bronchoconstriction)	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.	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.
Change in Chronic Disease Control by Measurement of Lung Function Through FEV1	1 month (between Visit 1 and Visit 2)	Change from Visit 1 in baseline FEV1,compared between patients on placebo vs ifetroban.
Clinical Improvement of Chronic Disease - Sino-Nasal Outcome Test (SNOT-22) Score	1 month (between Visit 1 and Visit 2)	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.
Aspirin-induced Leukotriene E4 (LTE4) Levels	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.	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.
Fractional Exhaled Nitric Oxide (FeNO)	1 month (between Visit 1 and Visit 2)	Change from Visit 1 in baseline FeNO levels at Visit 2, compared between patients on placebo vs ifetroban.
Change in Chronic Disease by Measurement of Asthma Control Through Asthma Control Questionnaire (ACQ) Score	1 month (between Visit 1 and Visit 2)	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.