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Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin) (Aspirin)

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ClinicalTrials.gov Identifier: NCT01597375
Recruitment Status : Completed
First Posted : May 14, 2012
Results First Posted : July 24, 2018
Last Update Posted : July 24, 2018
Sponsor:
Collaborator:
Brigham and Women's Hospital
Information provided by (Responsible Party):
Elliot Israel, MD, Brigham and Women's Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Supportive Care
Conditions Asthma, Aspirin-Induced
Aspirin Exacerbated Asthma
Interventions Drug: Placebo Oral Tablet
Drug: Prasugrel Oral Tablet
Enrollment 46
Recruitment Details A total of 51 potential participants were screened at Brigham and Women's Hospital.
Pre-assignment Details 46 of whom underwent randomization per protocol, and 40 of whom completed the trial and were analyzed.
Arm/Group Title Placebo Then Prasugrel Prasugrel Then Placebo
Hide Arm/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.

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.

Period Title: First Intervention (4 Weeks)
Started 23 23
Completed 21 22
Not Completed 2 1
Reason Not Completed
Uncontrolled Asthma             1             0
Needed surgery             1             0
Lost to Follow-up             0             1
Period Title: Washout (2 Weeks)
Started 21 22
Completed 20 22
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Period Title: Second Intervention
Started 20 22
Completed 19 21
Not Completed 1 1
Reason Not Completed
Failed to react at both Aspirin             1             1
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants who were randomized to receive either Prasugrel or Placebo oral tablets and who successfully completed both treatment assignments.
Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
<=18 years
0
   0.0%
Between 18 and 65 years
40
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants
47  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
24
  60.0%
Male
16
  40.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 40 participants
40
 100.0%
1.Primary Outcome
Title 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
Hide Description

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))

Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Prasugrel
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Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.
Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Overall Number of Participants Analyzed 43 42
Mean (Standard Error)
Unit of Measure: mg
79  (15) 139  (32)
2.Primary Outcome
Title 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.
Hide Description 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.
Time Frame Evaluated at visits 1 and 4 (weeks 4 and 22)
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Hide Analysis Population Description
The planned experimental protocol for COX-2 analysis at the lab bench was unsuccessful, therefore no data was collected for this Outcome Measure
Arm/Group Title Placebo Prasugrel
Hide Arm/Group Description:
Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.
Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo
Hide Description 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.
Time Frame Evaluated at visits 2 and 3 (weeks 8 and 14)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Prasugrel
Hide Arm/Group Description:
Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.
Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Overall Number of Participants Analyzed 43 42
Mean (Standard Error)
Unit of Measure: mg
109  (15) 164  (31)
4.Secondary Outcome
Title Change in Total Nasal Symptom Score(TNSS)From Baseline to Peak During Aspirin Challenge on Placebo Versus Prasugrel.
Hide Description 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).
Time Frame Data obtained at visits 2 and 3 (weeks 8 and 14) and change calculated at visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Prasugrel
Hide Arm/Group Description:
Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.
Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Overall Number of Participants Analyzed 43 42
Mean (Standard Error)
Unit of Measure: units on scale
7  (0.8) 6.5  (0.8)
5.Secondary Outcome
Title Change in Urinary LTE4 During Aspirin Challenge on Placebo Versus Prasugrel
Hide Description 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.
Time Frame Change from visits 2 at visit 3 (weeks 8, 14), calculated and reported at visit 3
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Prasugrel
Hide Arm/Group Description:
Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.
Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Overall Number of Participants Analyzed 43 42
Mean (Standard Deviation)
Unit of Measure: percentage change from baseline
37  (70) 19  (48)
6.Secondary Outcome
Title Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks
Hide Description 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 )
Time Frame Evaluated at baseline and reported at 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This was assessed across all participants with no planned comparisons between placebo and prasugrel.
Arm/Group Title Subjects With AERD Completing 8 Weeks of Aspirin Treatment
Hide Arm/Group Description:
Subjects with AERD who underwent Aspirin desensitization and 8 weeks of Aspirin treatment ( 650 mg of Aspirin twice daily )
Overall Number of Participants Analyzed 42
Mean (Standard Deviation)
Unit of Measure: parts per billion
15.8  (5.8)
7.Secondary Outcome
Title Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Score After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks
Hide Description 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 )
Time Frame Evaluated at baseline and reported at 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This was assessed across all participants with no planned comparisons between placebo and prasugrel.
Arm/Group Title Subjects With AERD Completing 8 Weeks of Aspirin Treatment
Hide Arm/Group Description:
Subjects with AERD who underwent Aspirin desensitization and 8 weeks of Aspirin treatment ( 650 mg of Aspirin twice daily )
Overall Number of Participants Analyzed 42
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.11  (0.11)
8.Secondary Outcome
Title Change From Baseline in Prostaglandin Metabolites (PGD-M) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks
Hide Description 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 )
Time Frame Evaluated at baseline and reported at 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
This was assessed across all participants with no planned comparisons between placebo and prasugrel.
Arm/Group Title Subjects With AERD Completing 8 Weeks of Aspirin Treatment
Hide Arm/Group Description:
Subjects with AERD who underwent Aspirin desensitization and 8 weeks of Aspirin treatment ( 650 mg of Aspirin twice daily )
Overall Number of Participants Analyzed 42
Mean (Standard Deviation)
Unit of Measure: ng/mg creatinine
-1.4957  (6.9651)
9.Other Pre-specified Outcome
Title Baseline Differences in Platelet Chemistry in Subjects With AERD Compared to Controls
Hide Description To determine if there are baseline differences in the percentages of activated platelets, platelet-leukocyte aggregates, or the plasma levels of soluble platelet products in subjects with AERD, compared to aspirin tolerant asthmatics (ATA) and non-asthmatic controls.
Time Frame Evaluated at visit 1 (week 4)
Outcome Measure Data Not Reported
10.Other Pre-specified Outcome
Title Effect of Prasugrel on Platelet Chemistry in Subjects With AERD During Aspirin Challenge.
Hide Description To determine if treatment with prasugrel changes the baseline percentages of activated platelets or platelet-leukocyte aggregates or changes the plasma levels of soluble platelet products during clinical reaction to aspirin
Time Frame Evaluated at visit 2 and 3 (week 8 and 14)
Outcome Measure Data Not Reported
Time Frame Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Prasugrel
Hide Arm/Group Description Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study. Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
All-Cause Mortality
Placebo Prasugrel
Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)      0/42 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Prasugrel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/43 (0.00%)      0/42 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Prasugrel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/43 (30.23%)      13/42 (30.95%)    
Blood and lymphatic system disorders     
Bruising   3/43 (6.98%)  3 12/42 (28.57%)  12
Lower leg edema   0/43 (0.00%)  0 1/42 (2.38%)  1
Ear and labyrinth disorders     
Ear Infection   0/43 (0.00%)  0 1/42 (2.38%)  1
Eye disorders     
Conjunctivitis   0/43 (0.00%)  0 1/42 (2.38%)  1
Gastrointestinal disorders     
Stomach Pain   1/43 (2.33%)  1 0/42 (0.00%)  0
Viral Gastroenteritis   0/43 (0.00%)  0 1/42 (2.38%)  1
Infections and infestations     
Throat Infection   1/43 (2.33%)  1 1/42 (2.38%)  1
Injury, poisoning and procedural complications     
Accidental ingestion of NSAID   1/43 (2.33%)  1 0/42 (0.00%)  0
Systematic Reaction to Aspirin Challenge   1/43 (2.33%)  1 0/42 (0.00%)  0
Spider Bite   1/43 (2.33%)  1 0/42 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle injury/Myalgia   1/43 (2.33%)  2 0/42 (0.00%)  0
Joint Stiffness   0/43 (0.00%)  0 1/42 (2.38%)  1
Nervous system disorders     
Headache   1/43 (2.33%)  2 1/42 (2.38%)  2
Finger tingling/Numbness   0/43 (0.00%)  0 1/42 (2.38%)  1
Light-Headedness   1/43 (2.33%)  1 0/42 (0.00%)  0
Psychiatric disorders     
Mood Change   1/43 (2.33%)  1 0/42 (0.00%)  0
Renal and urinary disorders     
Urinary Tract Infection   0/43 (0.00%)  0 1/42 (2.38%)  1
Respiratory, thoracic and mediastinal disorders     
Upper Respiratory Tract Infection/Sinusitis   5/43 (11.63%)  5 6/42 (14.29%)  7
Worsening of Asthma   5/43 (11.63%)  5 4/42 (9.52%)  4
Skin and subcutaneous tissue disorders     
Skin Rash   1/43 (2.33%)  1 1/42 (2.38%)  1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Tanya Laidlaw
Organization: Brigham and Women's Hospital
Phone: 617-525-1034
Responsible Party: Elliot Israel, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01597375     History of Changes
Other Study ID Numbers: 2010P002961
First Submitted: April 30, 2012
First Posted: May 14, 2012
Results First Submitted: May 30, 2018
Results First Posted: July 24, 2018
Last Update Posted: July 24, 2018