Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

Brigham and Women's Hospital38 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

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

Interventions

IfetrobanDRUG

4-week, double-blind, placebo-controlled parallel-design trial of oral ifetroban (a TP receptor antagonist) in patients with AERD

PlaceboDRUG

4-week, double-blind, placebo-controlled parallel-design trial of oral ifetroban (a TP receptor antagonist) in patients with AERD

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. 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) 3. Age between 18 and 70 years 4. No current smoking (not more than one instance of smoking in the last 3 months) 5. Non-pregnant Exclusion Criteria: 1. Hypersensitivity to montelukast 2. Current use of zileuton 3. History of bleeding diathesis or use of anticoagulant or antiplatelet drugs 4. Current use of any NSAIDs aside from the aspirin provided during the study 5. Current use of beta blockers 6. Use of any biologics within the last 4 months prior to initiating the study

Locations (1)

Asthma Research Center, Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

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

Time frame: 6 weeks from screening visit ( at visit 2)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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