Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03326063
• Collaborator: (none)
• Enrollment: 45
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 53.2
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Nasal Polyps; Asthma, Aspirin-Induced; Aspirin-exacerbated Respiratory Disease; Aspirin-Sensitive Asthma With Nasal Polyps	Drug: Ifetroban; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease
• Actual Study Start Date: Apr 26, 2018
• Anticipated Primary Completion Date: Oct 1, 2021
• Anticipated Study Completion Date: Oct 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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"

Secondary Outcome Measures

1. Bronchoconstriction during aspirin challenge [6 weeks from screening visit ( at visit 2)]

   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.

2. Aspirin-induced Leukotriene E4 (LTE4) levels [6 weeks from screening visit ( at visit 2)]

   Increase of urinary and nasal 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.

3. Clinical improvement of chronic disease - Forced Expiratory Volume 1 (FEV1) [1 month (between Visit 1 and Visit 2)]

   Change from Visit 1 in baseline FEV1,compared between patients on placebo vs ifetroban.

4. Clinical improvement of chronic disease - Asthma Control Questionnaire (ACQ) score [1 month (between Visit 1 and Visit 2)]

   Change from Visit 1 in baseline ACQ score, compared between patients on placebo vs ifetroban.

5. 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.

6. 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.

Other Outcome Measures

1. Urinary eicosanoid changes [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in levels of other urinary eicosanoids,from Visit 1 to Visit 2 pre-aspirin challenge and Visit 2 pre-aspirin to 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.

2. Nasal eicosanoid changes [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in levels of nasal eicosanoids, from Visit 1 to Visit 2 pre-aspirin challenge and Visit 2 pre-aspirin to 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.

3. Plasma/serum tryptase changes [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in levels of plasma/serum tryptase, from Visit 1 to Visit 2 pre-aspirin challenge and Visit 2 pre-aspirin to 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.

4. Nasal tryptase changes [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in levels of nasal tryptase, from Visit 1 to Visit 2 pre-aspirin challenge and Visit 2 pre-aspirin to 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.

5. Platelet activation - numbers of activated platelets [1 month (between Visit 1 and Visit 2) and during aspirin challenge visit]

   Change in numbers of activated platelets in the peripheral blood from Visit 1 to Visit 2 baseline (pre-aspirin administration) and during the aspirin-induced reaction at Visit 2 from Visit 2 baseline, compared between patients on placebo vs ifetroban, with the changes also analyzed with provocative aspirin dose as a covariate.

6. Platelet activation - percentages of activated platelets [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in percentages of activated platelets in the peripheral blood from Visit 1 to Visit 2 baseline (pre-aspirin administration) and during the aspirin-induced reaction at Visit 2 from Visit 2 baseline, compared between patients on placebo vs ifetroban, with the changes also analyzed with provocative aspirin dose as a covariate.

7. Platelet activation - numbers of platelet-leukocyte aggregates [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in numbers of platelet-leukocyte aggregates in the peripheral blood from Visit 1 to Visit 2 baseline (pre-aspirin administration) and during the aspirin-induced reaction at Visit 2 from Visit 2 baseline, compared between patients on placebo vs ifetroban, with the changes also analyzed with provocative aspirin dose as a covariate.

8. Platelet activation - percentages of platelet-leukocyte aggregates [1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)]

   Change in percentages of platelet-leukocyte aggregates in the peripheral blood from Visit 1 to Visit 2 baseline (pre-aspirin administration) and during the aspirin-induced reaction at Visit 2 from Visit 2 baseline, compared between patients on placebo vs ifetroban, with the changes also analyzed with provocative aspirin dose as a covariate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 COX inhibitors.

1. Stable asthma (post-bronchodilator 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)

2. Age between 18 and 70 years

3. No current smoking (not more than one instance of smoking in the last 3 months)

4. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asthma Research Center, Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Elliot Israel, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elliot Israel, MD, Director of Asthma Research Center, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT03326063
• Other Study ID Numbers: 2017P001523
• First Posted: Oct 30, 2017
• Last Update Posted: Mar 12, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Asthma; Respiration Disorders; Respiratory Tract Diseases; Nasal Polyps; Asthma, Aspirin-Induced; Polyps; Ifetroban

Study Results

No Results Posted as of Mar 12, 2021