Clinical trial NCT01597375: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)
Official title: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma, Aspirin-Induced
Aspirin Exacerbated Asthma
Keywords: Aspirin
Prasugrel
Asthma
AERD
Aspirin challenge
Aspirin desensitization
Aspirin induced asthma
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
First posted: 2012-05-14
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Primary outcomes:
measure: Difference in PD2 (Provocative Dose of Aspirin That Elicits an Increase in Nasal Symptom Score of 2 During an Aspirin Challenge) on Prasugrel Versus Placebo
timeFrame: Difference in PD2 (provocative dose of aspirin that elicits an increase in nasal symptom score of 2 during an aspirin challenge) between Visits 2 and 3 (weeks 8 and 14), calculated at visit 3
measure: Change From Baseline Expression Levels of COX-2 Transcript and Protein in Peripheral Blood Leukocytes of Subjects With AERD After 8 Weeks of Treatment With Aspirin.
timeFrame: Evaluated at visits 1 and 4 (weeks 4 and 22)
Secondary outcomes:
measure: Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo
timeFrame: Evaluated at visits 2 and 3 (weeks 8 and 14)
measure: Change in Total Nasal Symptom Score(TNSS)From Baseline to Peak During Aspirin Challenge on Placebo Versus Prasugrel.
timeFrame: Data obtained at visits 2 and 3 (weeks 8 and 14) and change calculated at visit 3
measure: Change in Urinary LTE4 During Aspirin Challenge on Placebo Versus Prasugrel
timeFrame: Change from visits 2 at visit 3 (weeks 8, 14), calculated and reported at visit 3
measure: Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks
timeFrame: Evaluated at baseline and reported at 8 weeks
measure: Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Score After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks
timeFrame: Evaluated at baseline and reported at 8 weeks
measure: Change From Baseline in Prostaglandin Metabolites (PGD-M) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks
timeFrame: Evaluated at baseline and reported at 8 weeks
Other outcomes:
measure: Baseline Differences in Platelet Chemistry in Subjects With AERD Compared to Controls
timeFrame: Evaluated at visit 1 (week 4)
measure: Effect of Prasugrel on Platelet Chemistry in Subjects With AERD During Aspirin Challenge.
timeFrame: Evaluated at visit 2 and 3 (week 8 and 14)
Locations:
city: Boston
country: United States
facility: Asthma Research Center
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brigham and Women's Hospital
name: Joshua Boyce, MD
role: PRINCIPAL_INVESTIGATOR
References: