Trial Outcomes & Findings for Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin) (NCT NCT01597375)

Last Updated: 2019-09-19

Results Overview

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))

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome 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

Results posted on

2019-09-19

Participant Flow

A total of 51 potential participants were screened at Brigham and Women's Hospital.

46 of whom underwent randomization per protocol, and 40 of whom completed the trial and were analyzed.

Participant milestones

Participant milestones
Measure	Placebo Then Prasugrel 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 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.
First Intervention (4 Weeks) STARTED	23	23
First Intervention (4 Weeks) COMPLETED	21	22
First Intervention (4 Weeks) NOT COMPLETED	2	1
Washout (2 Weeks) STARTED	21	22
Washout (2 Weeks) COMPLETED	20	22
Washout (2 Weeks) NOT COMPLETED	1	0
Second Intervention STARTED	20	22
Second Intervention COMPLETED	19	21
Second Intervention NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Then Prasugrel 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 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.
First Intervention (4 Weeks) Uncontrolled Asthma	1	0
First Intervention (4 Weeks) Needed surgery	1	0
First Intervention (4 Weeks) Lost to Follow-up	0	1
Washout (2 Weeks) Adverse Event	1	0
Second Intervention Failed to react at both Aspirin	1	1

Baseline Characteristics

Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=40 Participants Participants who were randomized to receive either Prasugrel or Placebo oral tablets and who successfully completed both treatment assignments.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	40 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	47 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Region of Enrollment United States	40 Participants n=5 Participants

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel n=42 Participants Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
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	79 mg Standard Error 15	139 mg Standard Error 32

PRIMARY outcome

Timeframe: Evaluated at visits 1 and 4 (weeks 4 and 22)

Population: The planned experimental protocol for COX-2 analysis at the lab bench was unsuccessful, therefore no data was collected for this Outcome Measure

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel n=42 Participants Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo	109 mg Standard Error 15	164 mg Standard Error 31

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel n=42 Participants Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Change in Total Nasal Symptom Score(TNSS)From Baseline to Peak During Aspirin Challenge on Placebo Versus Prasugrel.	7 units on scale Standard Error 0.8	6.5 units on scale Standard Error 0.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=43 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel n=42 Participants Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Change in Urinary LTE4 During Aspirin Challenge on Placebo Versus Prasugrel	37 percentage change from baseline Standard Deviation 70	19 percentage change from baseline Standard Deviation 48

SECONDARY outcome

Timeframe: Evaluated at baseline and reported at 8 weeks

Population: This was assessed across all participants with no planned comparisons between placebo and prasugrel.

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 )

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks	15.8 parts per billion Standard Deviation 5.8	—

SECONDARY outcome

Timeframe: Evaluated at baseline and reported at 8 weeks

Population: This was assessed across all participants with no planned comparisons between placebo and prasugrel.

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 )

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Score After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks	-0.11 score on a scale Standard Deviation 0.11	—

SECONDARY outcome

Timeframe: Evaluated at baseline and reported at 8 weeks

Population: This was assessed across all participants with no planned comparisons between placebo and prasugrel.

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 )

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Change From Baseline in Prostaglandin Metabolites (PGD-M) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks	-1.4957 ng/mg creatinine Standard Deviation 6.9651	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Evaluated at visit 1 (week 4)

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Evaluated at visit 2 and 3 (week 8 and 14)

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

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Prasugrel

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Tanya Laidlaw

Brigham and Women's Hospital

Phone: 617-525-1034

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=43 participants at risk Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study.	Prasugrel n=42 participants at risk Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study.
Blood and lymphatic system disorders Bruising	7.0% 3/43 • Number of events 3 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	28.6% 12/42 • Number of events 12 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection/Sinusitis	11.6% 5/43 • Number of events 5 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	14.3% 6/42 • Number of events 7 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Respiratory, thoracic and mediastinal disorders Worsening of Asthma	11.6% 5/43 • Number of events 5 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	9.5% 4/42 • Number of events 4 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Musculoskeletal and connective tissue disorders Muscle injury/Myalgia	2.3% 1/43 • Number of events 2 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Nervous system disorders Headache	2.3% 1/43 • Number of events 2 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 2 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Infections and infestations Throat Infection	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Injury, poisoning and procedural complications Accidental ingestion of NSAID	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Injury, poisoning and procedural complications Systematic Reaction to Aspirin Challenge	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Skin and subcutaneous tissue disorders Skin Rash	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Eye disorders Conjunctivitis	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Ear and labyrinth disorders Ear Infection	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Nervous system disorders Finger tingling/Numbness	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Musculoskeletal and connective tissue disorders Joint Stiffness	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Nervous system disorders Light-Headedness	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Blood and lymphatic system disorders Lower leg edema	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Psychiatric disorders Mood Change	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Injury, poisoning and procedural complications Spider Bite	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Gastrointestinal disorders Stomach Pain	2.3% 1/43 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	0.00% 0/42 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Renal and urinary disorders Urinary Tract Infection	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
Gastrointestinal disorders Viral Gastroenteritis	0.00% 0/43 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.	2.4% 1/42 • Number of events 1 • Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.