Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)
Condition: Asthma, Aspirin-Induced; Aspirin Exacerbated Asthma
MeSH terms: Asthma; Respiratory Tract Diseases; Respiration Disorders; Asthma, Aspirin-Induced
Intervention: Placebo Oral Tablet; Prasugrel Oral Tablet
Intervention description: Participants will take a 60 mg loading dose. After they will take 10 mg by mouth daily if they weigh >60kg or 5 mg by mouth daily if they weigh <60 kg. They will take the drug for 4 weeks prior to the aspirin challenge/desensitization.; Participants will take a 60 mg loading dose. After they will take 10 mg by mouth daily if they weigh >60kg or 5 mg by mouth daily if they weigh <60 kg. They will take the drug for 4 weeks prior to the aspirin challenge/desensitization.
Intervention MeSH terms: Prasugrel Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Aspirin; Prasugrel; Asthma; AERD; Aspirin challenge; Aspirin desensitization; Aspirin induced asthma

Summary:

      The investigators are doing this research study to find out if giving a drug called
      prasugrel, which is used to prevent blood clots, can reduce reactions to aspirin in people
      with aspirin exacerbated respiratory disease (AERD), and to learn why taking aspirin every
      day can work as a treatment for people with AERD. People with AERD have symptoms of asthma,
      severe runny nose, polyps in the nose, and develop allergic reactions if they take
      medications like aspirin.

      People with AERD can be desensitized to aspirin in order to be able to safely use it daily,
      but the investigators do not know if prasugrel may prevent reactions to aspirin and provide a
      safer way for people with AERD to tolerate aspirin.

      The investigators also want to understand what is different about the cells and urine from
      subjects who have AERD, in comparison to subjects who have asthma but do not have AERD and
      subjects who have allergic rhinitis but do not have asthma. Lastly, the investigators want to
      understand how aspirin acts differently in subjects who have AERD, in comparison to subjects
      who have asthma but do not have AERD.
    

Eligibility criteria:

        Inclusion Criteria for Participants with AERD:

          -  History of physician-diagnosed asthma

          -  History of nasal polyposis

          -  History of at least one clinical reaction to oral aspirin or other nonselective COX
             inhibitor with features of both lower (cough, chest tightness, wheezing, dyspnea) and
             upper (rhinorrhea, sneezing, nasal obstruction, conjunctival itching and discharge)
             airway involvement.

          -  Stable asthma (post-bronchodilator FEV1 of 70% or better, no increase in baseline dose
             of oral glucocorticoids for at least 3 months, and no history of hospitalization or
             emergency room visits for asthma for at least the prior 6 months).

          -  No current smoking, defined as no daily tobacco smoking for at least 6 months and not
             more than one instance of tobacco smoking in the last 3 months.

          -  Non-pregnant

          -  Only those individuals who would otherwise meet clinical qualifications for aspirin
             desensitization and treatment with high-dose aspirin will be considered for enrollment
             in the study.

        Inclusion Criteria for Participants who are Aspirin Tolerant Asthmatics:

          -  History of physician-diagnosed asthma.

          -  No current nasal polyposis confirmed by nasal examination.

          -  No history of any adverse reaction to aspirin or a COX inhibitor.

          -  Stable asthma (post-bronchodilator FEV1 of 70% or better, no increase in baseline dose
             of oral glucocorticoids for at least 3 months, and no history of hospitalization or
             emergency room visits for asthma for at least the prior 6 months).

          -  No current smoking

          -  Non-pregnant

        Inclusion Criteria for Non Asthmatics with Allergic Rhinitis:

          -  No history of physician-diagnosed asthma.

          -  No current nasal polyposis confirmed by nasal examination.

          -  No history of any adverse reaction to aspirin or a COX inhibitor.

          -  No current smoking

          -  Non-pregnant

          -  Clinical history of symptoms consistent with allergic rhinitis and previously
             documented allergy to at least one environmental,immunoglobulin E (IgE) testing).

          -  Normal lung function (baseline FEV1 of 80% of predicted or better).

          -  A score of 4 or below on the Asthma Screening Questionnaire (33) and negative
             responses to asthma history questions

        Exclusion Criteria for participants with AERD:

          -  Current breastfeeding

          -  History of bleeding diathesis or current use of anticoagulant or antiplatelet drugs

          -  Hypersensitivity to montelukast or thienopyridines

          -  History of peptic ulcer disease or gastrointestinal bleed

          -  Current severe gastro-esophageal reflux disease (GERD), defined as patient currently
             requiring more than 2 total doses of medication per day to treat persistent symptoms:
             either more than 2 doses of any single medication type (antacid, proton pump
             inhibitor, or H2 receptor antagonist), or more than 2 types of medication per day to
             treat symptoms

          -  History of systemic or life-threatening respiratory reaction to aspirin requiring
             intubation or administration of adrenalin

          -  Current use of any oral beta blocker (due to the risk of bronchospasm associated with
             beta blockers).

          -  History of transient ischemic attack or stroke, or diabetes.

          -  Current presence of uncontrolled hypertension.

          -  History of hepatic impairment or alcoholism, or evidence of abnormal liver function at
             Screening Visit. Aspartate transaminase (AST) and alanine transaminase (ALT) levels
             may not exceed 1.5x the upper limit of normal at Screening Visit (AST may not exceed
             52 IU/L, ALT may not exceed 78 IU/L).

        Exclusion Criteria for Participants with Aspirin Tolerant Asthma and Non Asthmatics with
        Allergic Rhinitis:

          -  Current breastfeeding

          -  History of bleeding diathesis or current use of anticoagulant or antiplatelet drugs

          -  Hypersensitivity to montelukast or thienopyridines

          -  History of peptic ulcer disease or gastrointestinal bleed

          -  Current severe GERD

          -  Current use of any oral beta blocker.