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Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

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ClinicalTrials.gov Identifier: NCT03326063
Recruitment Status : Recruiting
First Posted : October 30, 2017
Last Update Posted : May 31, 2018
Sponsor:
Information provided by (Responsible Party):
Elliot Israel, MD, Brigham and Women's Hospital

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 Type : Interventional  (Clinical Trial)
Estimated 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 : April 26, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

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 Name: 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




Primary Outcome Measures :
  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"


Secondary Outcome Measures :
  1. Bronchoconstriction during aspirin challenge [ Time Frame: 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 [ Time Frame: 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) [ 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. Clinical improvement of chronic disease - Asthma Control Questionnaire (ACQ) score [ Time Frame: 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 [ 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.

  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 Outcome Measures:
  1. Urinary 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 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 [ 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 COX inhibitors.
  2. 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)
  3. Age between 18 and 65 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03326063


Contacts
Contact: Tanya M Laidlaw, MD 617-525-1034 tlaidlaw@partners.org
Contact: Meghan Le 617-732-8201 mle8@bwh.harvard.edu

Locations
United States, Massachusetts
Asthma Research Center, Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Meghan Le    617-732-8201    mle8@bwh.harvard.edu   
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Elliot Israel, MD Brigham and Women's Hospital

Responsible Party: Elliot Israel, MD, Director of Asthma Research Center, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT03326063     History of Changes
Other Study ID Numbers: 2017P001523
First Posted: October 30, 2017    Key Record Dates
Last Update Posted: May 31, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
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:
Drug-Related Side Effects and Adverse Reactions
Asthma
Polyps
Respiration Disorders
Respiratory Tract Diseases
Nasal Polyps
Asthma, Aspirin-Induced
Bronchial Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathological Conditions, Anatomical
Nose Diseases
Otorhinolaryngologic Diseases
Drug Hypersensitivity
Chemically-Induced Disorders
Aspirin
Ifetroban
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents