Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

Nasal Polyps Clinical Trial

Official title:

Therapeutic Control of Aspirin-Exacerbated Respiratory Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03326063
• Other study ID #: 2017P001523
• Status: Completed
• Phase: Phase 2
• Start date: April 26, 2018
• Est. completion date: April 15, 2023

Study information

• Verified date: June 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: April 15, 2023
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Aspirin-exacerbated Respiratory Disease
• Aspirin-Sensitive Asthma With Nasal Polyps
• Asthma
• Asthma, Aspirin-Induced
• Nasal Polyps
• Polyps
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

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

Locations

Country	Name	City	State
United States	Asthma Research Center, Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent Change in Urinary Eicosanoid (TXB2 and LTE4) Levels	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. Measurements include urinary thromboxane B2 (TXB2) and LTE4.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Other	Nasal Eicosanoid Changes	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.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Other	Plasma/Serum Tryptase Changes	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.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Other	Nasal Tryptase Changes	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.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Other	Platelet Activation - Numbers of Activated Platelets	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.	1 month (between Visit 1 and Visit 2) and during aspirin challenge visit
Other	Platelet Activation - Percentages of Activated Platelets	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.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Other	Platelet Activation - Numbers of Platelet-leukocyte Aggregates	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.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Other	Platelet Activation - Percentages of Platelet-leukocyte Aggregates	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.	1 month (between Visit 1 and Visit 2) and 6 weeks from screening visit ( at visit 2)
Primary	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	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.
Secondary	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.
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)