ASAS: Diagnosis of Aspirin Hypersensitivity in Aspirin Exacerbated Respiratory Disease

Sponsor
Montefiore Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01320072
Collaborator
(none)
29
1
163
0.2

Study Details

Study Description

Brief Summary

To diagnose aspirin hypersensitivity in asthmatics by using and safe, low-dose aspirin oral challenge.

Hypothesis 1: A low dose of oral ASA (20 or 40 mg) will induce significantly different concentrations of arachidonic acid metabolites in ASA-sensitive asthmatics as compared to ASA-tolerant asthmatics.

Hypothesis 2: The low dose (20 or 40 mg) ASA challenge will be well tolerated by ASA-sensitive asthmatics.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    This research study is being conducted within the established Airway Research Group at Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, NY. The patient population in the Bronx has one of the highest asthma prevalences in the country. Thus, our study participants are being recruited among the population most in need of a better understanding of the disease process.

    Visits 1 and 2: Low-dose challenge with 20 mg and 40 mg of ASA. ASA will be administered orally to participants in both groups: 20 mg at Visit 1 and 40 mg at Visit 2. Visits will take place at least 1 week apart. Blood and urine will be collected at several time points.

    Visit 3: Oral graded ASA challenge will be performed to confirm or rule out the presence of ASA-hypersensitivity. This visit will take place at least 1 week after Visit 2. Both groups will undergo an oral graded ASA challenge as per earlier described protocol. Urine and plasma will be collected from the patients at several time points. Hypersensitivity reactions will be defined in four different ways: a) decline in forced expiratory volume in 1 second (FEV1) of at least 15% combined and naso-ocular reaction; b) 20% decline in FEV1; c) isolated naso-ocular reactions; d) isolated cutaneous reactions (hives and swelling). Patients with reactions will be treated according to their symptoms.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    29 participants
    Observational Model:
    Case-Control
    Time Perspective:
    Prospective
    Official Title:
    Diagnosis of Aspirin Hypersensitivity in Aspirin Exacerbated Respiratory Disease Using a Safe, Low Dose Aspirin Challenge
    Actual Study Start Date :
    May 1, 2010
    Actual Primary Completion Date :
    Oct 1, 2016
    Anticipated Study Completion Date :
    Dec 1, 2023

    Arms and Interventions

    Arm Intervention/Treatment
    Aspirin-sensitive asthmatics

    asthma patients with aspirin allergy

    aspirin-tolerant asthmatics

    asthma patients without aspirin allergy

    Outcome Measures

    Primary Outcome Measures

    1. Eicosanoid Metabolites Concentration [2 hours]

      eicosanoid metabolites concentration in plasma and urine 2 h post ASA challenge

    Secondary Outcome Measures

    1. Treatment-Related Adverse Events [24 hours after the challenge]

      Adverse reactions defined as bronchospasm requiring endotracheal intubation. The adverse reactions will be assessed through a post challenge follow-up with the patient at baseline and 24 hours after the challenge

    2. Change in Forced Expiratory Volume in One Second (FEV1) in Aspirin Exacerbated Respiratory Disease (AERD) Patients [12 months]

      We will assess FEV1% change from baseline at 12 months in AERD patients who have been on aspirin treatment for 12 months (current standard of care)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Participants of both sexes aged 18 years and older.

    2. Patients with a history of ASA-induced asthma who had at least one asthma attack after ingestion of aspirin or other NSAIDs.

    3. Patients with a history of ASA-tolerant asthma who had been occasionally using aspirin or other NSAIDs without any adverse reactions.

    Exclusion Criteria:
    1. Mental or legal incapacitation, or significant emotional problems, or a history of psychiatric disorders at the time of the enrollment.

    2. Pregnancy or breastfeeding at the time of enrollment.

    3. History of a severe anaphylactic reaction precipitated by ASA and/or other NSAIDs (such as ibuprofen, naproxen, indomethacin, Advil, Aleve, Motrin, diclofenac, etc.).

    4. History of a severe bronchospasm precipitated by ASA and/or other NSAIDs requiring an endotracheal intubation.

    5. Chronic kidney disease (a calculated GFR based on the Modification of Diet in Renal Disease (MDRD) equation is < 60 mL/min/1.73 sq.meter).

    6. Chronic liver disease by history and/or abnormal liver function tests (SGOT and SGPT ≥ 3 times above upper normal range).

    7. Baseline FEV1 < 70% (or < 1.5 L) of predicted, or an exacerbation of asthma in the 6 weeks preceding the study.

    8. An active infectious disease.

    9. Anemia that requires work-up, black stools, active bleeding.

    10. A history of gastrointestinal bleeding due to aspirin or other NSAIDS, gastritis, or duodenal ulcer not proven to be due to Helicobacter pylori.

    11. A history of hemophilia or any other bleeding disorder.

    12. Unstable angina.

    13. Participants taking aspirin and or other NSAIDs at the time of the study visits.

    14. Participants taking leukotriene receptors inhibitors or 5-lypooxygenase (5-LO) inhibitors at the time of the study visits.

    15. In addition, participants taking one or more of the following drugs intake last 14 days prior to the enrollment will be excluded: lithium, warfarine, enoxaparin, heparin, dalteparin, fluconazole, ketotifen. Short-acting antihistamines should be stopped 5 days before the challenge; long-acting antihistamines should be stopped 1 week prior to the challenge.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Montefiore Medical Center Bronx New York United States 10461

    Sponsors and Collaborators

    • Montefiore Medical Center

    Investigators

    • Principal Investigator: Elina Jerschow, MD, Attending physician

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Elina Jerschow, Attending physician, Montefiore Medical Center
    ClinicalTrials.gov Identifier:
    NCT01320072
    Other Study ID Numbers:
    • 10-01-002
    First Posted:
    Mar 22, 2011
    Last Update Posted:
    Jan 24, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Elina Jerschow, Attending physician, Montefiore Medical Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Arm/Group Description Patients with aspirin exacerbated respiratory disease, N=16 Aspirin tolerant asthma patients, N=13
    Period Title: Overall Study
    STARTED 16 13
    COMPLETED 16 13
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics Total
    Arm/Group Description patients with aspirin exacerbated respiratory disease aspirin-tolerant patients with asthma Total of all reporting groups
    Overall Participants 16 13 29
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    16
    100%
    13
    100%
    29
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    37.8
    (3.2)
    42.6
    (2.4)
    40.3
    (2.9)
    Sex: Female, Male (Count of Participants)
    Female
    10
    62.5%
    7
    53.8%
    17
    58.6%
    Male
    6
    37.5%
    6
    46.2%
    12
    41.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    7.7%
    1
    3.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    9
    56.3%
    8
    61.5%
    17
    58.6%
    White
    7
    43.8%
    4
    30.8%
    11
    37.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    16
    100%
    13
    100%
    29
    100%

    Outcome Measures

    1. Primary Outcome
    Title Eicosanoid Metabolites Concentration
    Description eicosanoid metabolites concentration in plasma and urine 2 h post ASA challenge
    Time Frame 2 hours

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Arm/Group Description Patients with aspirin exacerbated respiratory disease, N=16 Aspirin tolerant asthma patients, N=13
    Measure Participants 16 13
    Mean (Standard Error) [log-pg/mg creatinine]
    6.91
    (0.15)
    5.8
    (0.12)
    2. Secondary Outcome
    Title Treatment-Related Adverse Events
    Description Adverse reactions defined as bronchospasm requiring endotracheal intubation. The adverse reactions will be assessed through a post challenge follow-up with the patient at baseline and 24 hours after the challenge
    Time Frame 24 hours after the challenge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Arm/Group Description Patients with aspirin exacerbated respiratory disease, N=16 Aspirin tolerant asthma patients, N=13
    Measure Participants 16 13
    Number [participants]
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Change in Forced Expiratory Volume in One Second (FEV1) in Aspirin Exacerbated Respiratory Disease (AERD) Patients
    Description We will assess FEV1% change from baseline at 12 months in AERD patients who have been on aspirin treatment for 12 months (current standard of care)
    Time Frame 12 months

    Outcome Measure Data

    Analysis Population Description
    AERD patients will continue aspirin treatment for 12 months and the change from baseline in their FEV1% predicted will be monitored during this time
    Arm/Group Title Aspirin-sensitive Asthmatics
    Arm/Group Description Asthma patients with aspirin exacerbated respiratory disease
    Measure Participants 16
    Mean (Standard Error) [change in percent predicted FEV1]
    12
    (1.1)

    Adverse Events

    Time Frame 12 hours
    Adverse Event Reporting Description patients will be assessed for adverse reactions during their aspirin challenge (standard of care)
    Arm/Group Title Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Arm/Group Description Patients with aspirin exacerbated respiratory disease, N=16 Aspirin tolerant asthma patients, N=13
    All Cause Mortality
    Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/13 (0%)
    Other (Not Including Serious) Adverse Events
    Aspirin-sensitive Asthmatics Aspirin-tolerant Asthmatics
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/13 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE 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 Dr. Elina Jerschow, attending physician
    Organization Montefiore Medical Center
    Phone 9173625291
    Email ejerscho@montefiore.org
    Responsible Party:
    Elina Jerschow, Attending physician, Montefiore Medical Center
    ClinicalTrials.gov Identifier:
    NCT01320072
    Other Study ID Numbers:
    • 10-01-002
    First Posted:
    Mar 22, 2011
    Last Update Posted:
    Jan 24, 2022
    Last Verified:
    Jan 1, 2022