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Completed

NCT Number: NCT03326063

Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

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).

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Key information

Conditions

Nasal Polyps Aspirin-Sensitive Asthma With Nasal Polyps Aspirin-exacerbated Respiratory Disease Asthma Asthma, Aspirin-Induced Bronchial Diseases Chemically-Induced Disorders Drug Hypersensitivity Drug-Related Side Effects and Adverse Reactions Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Nose Diseases Otorhinolaryngologic Diseases Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Polyps Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Asthma Research Center, Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ifetroban

Drug

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

Drug

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

Primary outcomes

  1. Provocative Dose 2 (PD2) During Aspirin Challenge

    Time frame: 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 outcomes

  1. Percentage Change From Baseline of FEV1 During Aspirin Challenge (Bronchoconstriction)

    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.

    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.

  2. Aspirin-induced Leukotriene E4 (LTE4) Levels

    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.

    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.

  3. Change in Chronic Disease Control by Measurement of Lung Function Through FEV1

    Time frame: 1 month (between Visit 1 and Visit 2)

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

  4. Change in Chronic Disease by Measurement of Asthma Control Through Asthma Control Questionnaire (ACQ) Score

    Time frame: 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.

  5. Clinical Improvement of Chronic Disease - Sino-Nasal Outcome Test (SNOT-22) Score

    Time frame: 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.

  6. Fractional Exhaled Nitric Oxide (FeNO)

    Time frame: 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 outcomes

  1. Percent Change in Urinary Eicosanoid (TXB2 and LTE4) Levels

    Time frame: 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. Measurements include urinary thromboxane B2 (TXB2) and LTE4.

  2. Nasal Eicosanoid Changes

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Registry information

Official study title

Therapeutic Control of Aspirin-Exacerbated Respiratory Disease

Important dates

Study start
2018
Primary completion
2022
Study completion
2023
First posted
Oct 30, 2017
Registry last updated
Jul 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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