Diagnosis of Aspirin Hypersensitivity in Aspirin Exacerbated Respiratory Disease

Terminated

• Conditions: Asthma, Aspirin-induced

• Registration Number: NCT01320072
• Lead Sponsor: Montefiore Medical Center

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.

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 Timeline

• Study Start: 2010-05
• Study First Submitted: 2011-03-17
• Study First Submitted QC: 2011-03-18
• Study First Posted: 2011-03-22
• Results First Submitted: 2016-01-08
• Results First Submitted QC: 2016-04-03
• Results First Posted: 2016-04-05
• Primary Completion: 2016-10
• Study Completion: 2022-05-26
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-15
• Last Update Posted: 2023-02-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Eicosanoid Metabolites Concentration	2 hours	eicosanoid metabolites concentration in plasma and urine 2 h post ASA challenge

Secondary Outcome Measures

Name	Time	Method
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)
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

Trial Locations

Locations (1)

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States