Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

Phase 2

Completed

Conditions: Asthma, Aspirin-Induced
Aspirin Exacerbated Asthma

Interventions: Drug: Placebo Oral Tablet
Drug: Prasugrel Oral Tablet

Registration Number: NCT01597375

Lead Sponsor: Elliot Israel, MD

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 Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo then Prasugrel	Prasugrel Oral Tablet	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.
Prasugrel then Placebo	Prasugrel Oral Tablet	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.
Placebo then Prasugrel	Placebo Oral Tablet	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.
Prasugrel then Placebo	Placebo Oral Tablet	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.

Primary Outcome Measures

Name	Time	Method
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	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	The PD2 is the provocative dose of aspirin that elicits an increase in nasal symptom score of 2 during an aspirin challenge. The PD2 is calculated by: inverse〖log〗_10 (((2-(PrevTNSS-BaselineTNSS))×(〖log〗_10 ProvocDose-〖log〗_10 PrevDose))/((MaxTNSS-BaselineTNSS)-(PrevTNSS-BaselineTNSS) )+(〖log〗_10 PrevDose))
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.	Evaluated at visits 1 and 4 (weeks 4 and 22)	This study 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Score After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks	Evaluated at baseline and reported at 8 weeks	We will note difference in the Asthma Control Questionnaire-7 (ACQ-7) score \[ The ACQ has 7 questions on a 7-point scale (minimum score of 0=no impairment, maximum score of 6= maximum impairment)\] obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily )
Change in Total Nasal Symptom Score(TNSS)From Baseline to Peak During Aspirin Challenge on Placebo Versus Prasugrel.	Data obtained at visits 2 and 3 (weeks 8 and 14) and change calculated at visit 3	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 including congestion, rhinorrhea, runny nose, itchy nose, sneezing, itchy eyes, teary eyes, itchy ears/throat, and eye redness were assessed on a 0- to 5-point scale (0, none-5, very severe) in response to the provocative dose of aspirin during aspirin challenge/desensitization and summed together to generate the TNSS score (range 0-40).
Change From Baseline in Prostaglandin Metabolites (PGD-M) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks	Evaluated at baseline and reported at 8 weeks	We will note difference in the Prostaglandin metabolites (PGD-M) measurement obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily )
Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo	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 During Aspirin Challenge on Placebo Versus Prasugrel	Change from visits 2 at visit 3 (weeks 8, 14), calculated and reported at visit 3	We will compare the participant's Leukotriene E4 (LTE4) obtained from the aspirin challenge done after pretreatment with prasugrel, the aspirin challenge done after pretreatment with placebo.
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks	Evaluated at baseline and reported at 8 weeks	We will note difference in the fractional exhaled nitric oxide (FeNO) obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily )