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Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Brigham and Women's Hospital
Sponsor:
Collaborator:
Brigham and Women's Hospital
Information provided by (Responsible Party):
Elliot Israel, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01597375
First received: April 30, 2012
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Asthma, Aspirin-Induced
Aspirin Exacerbated Asthma
Drug: Prasugrel

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Supportive Care
Official Title: Therapeutic Control of Aspirin-Exacerbated Respiratory Disease (Aspirin)

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Change in Total Nasal Symptom Score(TNSS)from baseline to aspirin challenge/desensitization. [ Time Frame: Evaluated at Visits 0-3 (weeks -1, 4, 8) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 115
Study Start Date: August 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo/Prasugrel
Subjects with AERD taking placebo prior to their first aspirin challenge/desensitization and prasugrel before their second aspirin challenge/desensitization.
Drug: Prasugrel
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.
Other Name: Effient
Prasugrel/Placebo
Subjects with AERD taking prasugrel prior to their first aspirin challenge/desensitization and placebo before their second aspirin challenge/desensitization.
Drug: Prasugrel
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.
Other Name: Effient

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Participants with AERD:

  • 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.

Inclusion Criteria for Participants who are Aspirin Tolerant Asthmatics:

  • 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

Inclusion Criteria for Non Asthmatics with Allergic Rhinitis:

  • No 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.
  • No current smoking
  • Non-pregnant
  • Clinical history of symptoms consistent with allergic rhinitis and previously documented allergy to at least one environmental,immunoglobulin E (IgE) testing).
  • Normal lung function (baseline FEV1 of 80% of predicted or better).
  • A score of 4 or below on the Asthma Screening Questionnaire (33) and negative responses to asthma history questions

Exclusion Criteria for participants with AERD:

  • 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).

Exclusion Criteria for Participants with Aspirin Tolerant Asthma and Non Asthmatics with Allergic Rhinitis:

  • 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
  • Current use of any oral beta blocker.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01597375

Contacts
Contact: Jillian Bensko 617-732-6641 jbensko@partners.org

Locations
United States, Massachusetts
Asthma Research Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jillian Bensko    617-732-6641    jbensko@partners.org   
Principal Investigator: Elliot Israel, MD         
Sponsors and Collaborators
Elliot Israel, MD
Brigham and Women's Hospital
Investigators
Principal Investigator: Elliot Israel, MD Brigham and Women's Hospital
Principal Investigator: Joshua Boyce, MD Brigham and Women's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Elliot Israel, MD, Director of the Asthma Research Center, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01597375     History of Changes
Other Study ID Numbers: 2010P002961
Study First Received: April 30, 2012
Last Updated: July 16, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Brigham and Women's Hospital:
Aspirin
Prasugrel
Asthma
AERD
Aspirin challenge
Aspirin desensitization
Aspirin induced asthma

Additional relevant MeSH terms:
Drug Hypersensitivity
Asthma
Asthma, Aspirin-Induced
Respiration Disorders
Respiratory Tract Diseases
Bronchial Diseases
Chemically-Induced Disorders
Drug-Related Side Effects and Adverse Reactions
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Aspirin
Prasugrel
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 24, 2014