Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

Elliot Israel, MD

Status and phase: Completed; Phase 2

Conditions: Aspirin Exacerbated Asthma; Asthma, Aspirin-Induced

Treatments: Drug: Prasugrel Oral Tablet; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT01597375

2010P002961

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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46 participants in 2 patient groups

Placebo then Prasugrel

Experimental group

Description:

Subjects with AERD first received placebo oral tablet for 4 weeks prior to their aspirin challenge/desensitization. After aspirin challenge/desensitization subjects were discharged to home to washout the study drug from the first treatment phase. At the end of the 2-week washout period, subjects crossed over to the alternate treatment for 4 weeks of Prasugrel oral tablets \[ (5 mg (for patients \<60kg) or 10mg (\> 60kg) daily, following a 60mg loading dose)\] and returned for the second aspirin challenge. Because no period effect was observed, data obtained from all subjects while on placebo from either visit 2 or 3 were combined.

Treatment:

Drug: Placebo Oral Tablet

Drug: Prasugrel Oral Tablet

Prasugrel then Placebo

Experimental group

Description:

Subjects with AERD first received prasugrel oral tablets \[ (5 mg (for patients \<60kg) or 10mg (\> 60kg) daily, following a 60mg loading dose)\] prior to their aspirin challenge/desensitization. After aspirin challenge/desensitization subjects were discharged to home to washout the study drug from the first treatment phase. At the end of the 2-week washout period, subjects crossed over to the alternate treatment for 4 weeks of Placebo oral tablet. Because no period effect was observed, data obtained from all subjects while on Prasugrel from either visit 2 or 3 were combined.

Treatment:

Drug: Placebo Oral Tablet

Drug: Prasugrel Oral Tablet