Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

NCT01597375 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2010P002961
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma, Aspirin-Induced; Aspirin Exacerbated Asthma

Keywords

Aspirin; Prasugrel; Asthma; AERD; Aspirin challenge; Aspirin desensitization; Aspirin induced asthma

Outcome Measures

Primary Outcomes (2)

• 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

  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))

  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

• 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.

  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.

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

Secondary Outcomes (6)

• Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo

  Evaluated at visits 2 and 3 (weeks 8 and 14)

• 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

• 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

• 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

• 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

Other Outcomes (2)

• Baseline Differences in Platelet Chemistry in Subjects With AERD Compared to Controls

  Evaluated at visit 1 (week 4)

• Effect of Prasugrel on Platelet Chemistry in Subjects With AERD During Aspirin Challenge.

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

Study Arms (2)

Placebo then Prasugrel

EXPERIMENTAL

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.

Drug: Placebo Oral Tablet; Drug: Prasugrel Oral Tablet

Prasugrel then Placebo

EXPERIMENTAL

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.

Drug: Placebo Oral Tablet; Drug: Prasugrel Oral Tablet

Interventions

Placebo Oral Tablet DRUG

Participants will take a 60 mg loading dose. After they will take 10 mg by mouth daily if they weigh \>60kg or 5 mg by mouth daily if they weigh \<60 kg. They will take the drug for 4 weeks prior to the aspirin challenge/desensitization.

Also known as: Placebo

Placebo then Prasugrel; Prasugrel then Placebo

Prasugrel Oral Tablet DRUG

Participants will take a 60 mg loading dose. After they will take 10 mg by mouth daily if they weigh \>60kg or 5 mg by mouth daily if they weigh \<60 kg. They will take the drug for 4 weeks prior to the aspirin challenge/desensitization.

Also known as: Effient

Placebo then Prasugrel; Prasugrel then Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• No history of physician-diagnosed asthma.
• No current nasal polyposis confirmed by nasal examination.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Elliot Israel, MD: lead
• Brigham and Women's Hospital: collaborator

Study Sites (1)

Asthma Research Center

Boston, Massachusetts, 02115, United States

Location

Related Links

• Click here for more info.

MeSH Terms

Conditions

Asthma, Aspirin-Induced; Asthma

Interventions

Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Tanya Laidlaw
• Organization: Brigham and Women's Hospital

tlaidlaw@bwh.harvard.edu

617-525-1034

Study Officials

• Elliot Israel, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Joshua Boyce, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Asthma Research Center

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: May 14, 2012
• Study Start: August 31, 2012
• Primary Completion: December 14, 2016
• Study Completion: December 14, 2016
• Last Updated: September 19, 2019
• Results First Posted: July 24, 2018

Record last verified: 2019-09

Locations

US (1)