Clinical Trial: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

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.

Detailed Summary:
Sponsor: Elliot Israel, MD

Current Primary Outcome:

• Effect of prasugrel on PD2 in an aspirin challenge [ Time Frame: Evaluated at Visits 2 and 3 (weeks 8 and 14) ]
  To determine whether blocking P2Y12 receptors attenuates the severity of upper respiratory reactions to aspirin ingestion in individuals with AERD.
• 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. [ Time Frame: Evaluated at visits 1 and 4 (weeks 4 and 22) ]
  This study has two parts. The primary analysis for part 2 will compare this outcome within each participant between baseline (established at Visit 1, prior to initiation of prasugrel therapy) and at the completion of 8 weeks of aspirin therapy. In secondary analysis, we will compare the AERD participant group to the Aspirin Tolerant Asthmatic (ATA) group with respect to the changes in COX-2 expression levels in peripheral blood leukocytes induced by 8 weeks of aspirin treatment to determine if aspirin-induced changes are specific to AERD.

Original Primary Outcome:

• Change in Total Nasal Symptom Score(TNSS)from baseline to aspirin challenge/desensitization. [ Time Frame: Evaluated at Visits 0-3 (weeks -1, 4, 8) ]
  This study has two parts. The primary outcome in Part 1 will be the maximum Total Nasal Symptom Score (TNSS) attained for subjects with AERD during the clinical reaction to aspirin challenge. The primary analysis will compare this outcome within each participant after treatment with prasugrel versus placebo. Nasal symptoms (congestion, rhinorrhea, itching, and sneezing) in response to the provocative dose of aspirin during aspirin challenge/desensitization will be monitored based on a 0- to 5-point scale (0, none-5, very severe).
• 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. [ Time Frame: Evaluated at visits 1 and 4 (weeks 4 and 22) ]
  This study has two parts. The primary analysis for part 2 will compare this outcome within each participant between baseline (established at Visit 1, prior to initiation of prasugrel therapy) and at the completion of 8 weeks of aspirin therapy. In secondary analysis, we will compare the AERD participant group to the ATA group with respect to the changes in COX-2 expression levels in peripheral blood leukocytes induced by 8 weeks of aspirin treatment to determine if aspirin-induced changes are specific to AERD.

Current Secondary Outcome:

• Difference in participant's provocative dose of aspirin when pretreated with prasugrel versus placebo [ Time Frame: Evaluated at visits 2 and 3 (weeks 8 and 14) ]
  We will monitor the dose of aspirin at which the participant shows symptoms (increased discomfort, 15% drop in FEV1) during the aspirin challenge/desensitization. We will compare the provocative aspirin dose obtained from the aspirin challenge occurring after pretreatment with prasugrel to the dose obtained after pretreatment with placebo.
• Change in Total Nasal Symptom Score(TNSS)from baseline to aspirin challenge/desensitization. [ Time Frame: Evaluated at Visits 0-3 (weeks -1, 4, 8) ]
  This study has two parts. The primary outcome in Part 1 will be the maximum Total Nasal Symptom Score (TNSS) attained for subjects with AERD during the clinical reaction to aspirin challenge. The primary analysis will compare this outcome within each participant after treatment with prasugrel versus placebo. Nasal symptoms (congestion, rhinorrhea, itching, and sneezing) in response to the provocative dose of aspirin during aspirin challenge/desensitization will be monitored based on a 0- to 5-point scale (0, none-5, very severe).
• Change in urinary LTE4 [ Time Frame: Evaluated at visits 1-4 (weeks 4, 8, 14, 22) ]
  We will compare the participant's Leukotriene E4 (LTE4) obtained at baseline with the LTE4 obtained from the aspirin challenge done after pretreatment with prasugrel, the aspirin challenge done after pretreatment with placebo, and lastly the LTE4 obtained after 8 weeks on aspirin. We will also compare the levels of LTE4 of participants with AERD to those obtained from participants who have aspirin tolerant asthma and those with allergic rhinitis (no asthma).
• Effect desensitization to and treatment with aspirin has on baseline characteristics of AERD [ Time Frame: Evaluated at visits 1, 2, 3, 4 (weeks 4, 8, 14, 22) ]
  We will note differences in the asthma control test, prostaglandin (PG) metabolites, fractional exhaled nitric oxide (FeNO) obtained before any treatment, after treatment with prasugrel, after treatment with placebo, and after treatment with aspirin for 8 weeks.

Original Secondary Outcome:

• Difference in participant's provocative dose of aspirin when pretreated with prasugrel versus placebo [ Time Frame: Evaluated at visits 2 and 3 (weeks 8 and 14) ]
  We will monitor the dose of aspirin at which the participant shows symptoms (increased discomfort, 15% drop in FEV1) during the aspirin challenge/desensitization. We will compare the provocative aspirin dose obtained from the aspirin challenge occurring after pretreatment with prasugrel to the dose obtained after pretreatment with placebo.
• Change in urinary LTE4 [ Time Frame: Evaluated at visits 1-4 (weeks 4, 8, 14, 22) ]
  We will compare the participant's LTE4 obtained at baseline with the LTE4 obtained from the aspirin challenge done after pretreatment with prasugrel, the aspirin challenge done after pretreatment with placebo, and lastly the LTE4 obtained after 8 weeks on aspirin. We will also compare the levels of LTE4 of participants with AERD to those obtained from participants who have aspirin tolerant asthma and those with allergic rhinitis (no asthma).
• Effect desensitization to and treatment with aspirin has on baseline characteristics of AERD [ Time Frame: Evaluated at visits 1, 2, 3, 4 (weeks 4, 8, 14, 22) ]
  We will note differences in the asthma control test, PG metabolites, FeNO obtained before any treatment, after treatment with prasugrel, after treatment with placebo, and after treatment with aspirin for 8 weeks.

Dates:
Date Received: April 30, 2012
Date Started: August 2012
Date Completion: March 2017
Last Updated: January 4, 2017
Last Verified: January 2017