Clinical trial NCT03326063: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban
Official title: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nasal Polyps
Asthma, Aspirin-Induced
Aspirin-exacerbated Respiratory Disease
Aspirin-Sensitive Asthma With Nasal Polyps
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2017-10-30
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Provocative Dose 2 (PD2) During Aspirin Challenge
timeFrame: 6 weeks from screening visit ( at visit 2)
Secondary outcomes:
measure: Percentage Change From Baseline of FEV1 During Aspirin Challenge (Bronchoconstriction)
timeFrame: 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.
measure: Aspirin-induced Leukotriene E4 (LTE4) Levels
timeFrame: 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.
measure: Change in Chronic Disease Control by Measurement of Lung Function Through FEV1
timeFrame: 1 month (between Visit 1 and Visit 2)
measure: Change in Chronic Disease by Measurement of Asthma Control Through Asthma Control Questionnaire (ACQ) Score
timeFrame: 1 month (between Visit 1 and Visit 2)
measure: Clinical Improvement of Chronic Disease - Sino-Nasal Outcome Test (SNOT-22) Score
timeFrame: 1 month (between Visit 1 and Visit 2)
measure: Fractional Exhaled Nitric Oxide (FeNO)
timeFrame: 1 month (between Visit 1 and Visit 2)
Other outcomes:
measure: Percent Change in Urinary Eicosanoid (TXB2 and LTE4) Levels
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
measure: Nasal Eicosanoid Changes
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
measure: Plasma/Serum Tryptase Changes
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
measure: Nasal Tryptase Changes
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
measure: Platelet Activation - Numbers of Activated Platelets
timeFrame: 1 month (between Visit 1 and Visit 2) and during aspirin challenge visit
measure: Platelet Activation - Percentages of Activated Platelets
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
measure: Platelet Activation - Numbers of Platelet-leukocyte Aggregates
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
measure: Platelet Activation - Percentages of Platelet-leukocyte Aggregates
timeFrame: 1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Locations:
city: Boston
country: United States
facility: Asthma Research Center, Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
References: