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Long-term Aspirin Therapy as a Predictor of Decreased Susceptibility to SARS-CoV-2 Infection in Aspirin-Exacerbated Respiratory Disease (AERD-CoV19)

Primary Purpose

AERD - Aspirin Exacerbated Respiratory Disease

Status
Recruiting
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Aspirin 300 Mg Oral Tablet
Placebo
Sponsored by
Lucyna Mastalerz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for AERD - Aspirin Exacerbated Respiratory Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: INCLUSION CRITERIA FOR AERD PATIENTS: signed informed consent form 18-70 years old AERD patients with baseline FEV1 of at least 70% of the predicted value on the challenge/desensitization day no pregnancy, higly effective contraception must be used INCLUSION CRITERIA FOR HEALTHY CONTROL: signed informed consent form 18-70 years old and healthy condition no asthma Exclusion Criteria: failure of the circulatory and respiratory system, liver, kidneys and other vital organs diabetes, cancer, systemic diseases of connective tissue, infectious diseases, coagulation disorders, active peptic ulcer disease, any active bleeding process. Use of drugs that interact with aspirin use of intoxicants, alcohol abuse, active and passive smoking, pregnancy, lactation. hypersensitivity to the active substance or any of the excipients

Sites / Locations

  • University Hospital, Pulmunology ClinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Aspirin

Placebo

Arm Description

Acard 300 mg (Acidum acetylsalicylicum). 1 tablet (300 mg) twice a day

Placebo 1 tablet twice a day

Outcomes

Primary Outcome Measures

Number of Participants with two-fold decrease in gene expression of ACE2, TMPRSS2, BSG, PPIA, PPIB, DPP4, IFNA1, IFNB1 IFNG, IFNL1, IFNL2 and ISG in sputum and nasal cells after 8 weeks of placebo/aspirin therapy compared to the baseline value.

Secondary Outcome Measures

Full Information

First Posted
March 1, 2023
Last Updated
April 4, 2023
Sponsor
Lucyna Mastalerz
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1. Study Identification

Unique Protocol Identification Number
NCT05797597
Brief Title
Long-term Aspirin Therapy as a Predictor of Decreased Susceptibility to SARS-CoV-2 Infection in Aspirin-Exacerbated Respiratory Disease
Acronym
AERD-CoV19
Official Title
Long-term Aspirin Therapy as a Predictor of Decreased Susceptibility to SARS-CoV-2 Infection in Aspirin-Exacerbated Respiratory Disease
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 7, 2022 (Actual)
Primary Completion Date
February 28, 2025 (Anticipated)
Study Completion Date
February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lucyna Mastalerz

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Aspirin-exacerbated respiratory disease (AERD) is characterized by the presence of asthma, chronic rhinosinusitis with nasal polyposis (CRwNP), and acute respiratory reactions induced by aspirin and other cyclooxygenase-1 inhibitors. One of the well-established therapeutic options is aspirin desensitization followed by daily aspirin therapy. The potential mechanisms underlying the clinical benefit of this approach include the downregulation of CysLT1 receptor, inhibition of PGD2 and interleukin IL-4 via the signal transducer and activator of transcription 6, global (blood, urine) activation of type 2 (T2) inflammation as well as local (sputum) reduction of T2 asthma inflammation. Indeed, among current aspirin-treated patients with AERD (n=37), no one had severe acute respiratory syndrome coronavirus clade 2 (SARS CoV-2) infection and most importantly, none of them developed COVID19 during pandemic. WHY? Notably, patients with AERD did not have asthma and nasal polyps exacerbation on aspirin, which is in line with other studies. Respiratory infections, such as the current COVID-19 pandemic, target epithelial cells in the respiratory tract. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. Nasal and bronchial epithelium play a key role in the early phases of an immune response to respiratory viruses. Induced sputum (IS) and nasal lavage (NL) cells are likely the first immune cells to encounter SARS CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first mediators produced upon viral infection. IFNs are divided into three groups based on their receptor usage; type I IFNs (IFN-α and IFN-β), type II IFN (IFN-γ), and type III IFNs (IFN-λ1 and 2). Both production of IFN and cellular response to IFN are critical steps for the restriction of viral dissemination. An interferon-stimulated gene (ISG) is a gene whose expression is stimulated by interferon. Specifically, type I and type III interferons are antiviral cytokines, triggering ISGs that combat viral infections. The type II interferon class only has one cytokine (IFN-γ), which has some antiviral activity. To conclude, the assessment of gene expression for interferon α1 (IFNA1), interferon β1 (IFNB1), interferon γ (IFNG), interferon λ1 and λ2 (IFNL1 and IFNL2) as well as for ACE2 and TMPRSS2 in sputum and nasal cells may shed new light on the course of this infection in patient with AERD during long term aspirin therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
AERD - Aspirin Exacerbated Respiratory Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
76 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aspirin
Arm Type
Experimental
Arm Description
Acard 300 mg (Acidum acetylsalicylicum). 1 tablet (300 mg) twice a day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo 1 tablet twice a day
Intervention Type
Drug
Intervention Name(s)
Aspirin 300 Mg Oral Tablet
Intervention Description
8-week treatment of aspirin, then after 2-weeks washout the next treatment arm is placebo for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
8-week treatment of placebo, then after 2-weeks washout the next treatment arm is aspirin for 8 weeks
Primary Outcome Measure Information:
Title
Number of Participants with two-fold decrease in gene expression of ACE2, TMPRSS2, BSG, PPIA, PPIB, DPP4, IFNA1, IFNB1 IFNG, IFNL1, IFNL2 and ISG in sputum and nasal cells after 8 weeks of placebo/aspirin therapy compared to the baseline value.
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: INCLUSION CRITERIA FOR AERD PATIENTS: signed informed consent form 18-70 years old AERD patients with baseline FEV1 of at least 70% of the predicted value on the challenge/desensitization day no pregnancy, higly effective contraception must be used INCLUSION CRITERIA FOR HEALTHY CONTROL: signed informed consent form 18-70 years old and healthy condition no asthma Exclusion Criteria: failure of the circulatory and respiratory system, liver, kidneys and other vital organs diabetes, cancer, systemic diseases of connective tissue, infectious diseases, coagulation disorders, active peptic ulcer disease, any active bleeding process. Use of drugs that interact with aspirin use of intoxicants, alcohol abuse, active and passive smoking, pregnancy, lactation. hypersensitivity to the active substance or any of the excipients
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lucyna Mastalerz, prof.
Phone
12 40 03 050
Email
lucyna.mastalerz@uj.edu.pl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucyna Mastalerz, prof.
Organizational Affiliation
Jagiellonian University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital, Pulmunology Clinic
City
Kraków
ZIP/Postal Code
30-688
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucyna Mastalerz, prof.
Phone
12 40 03 050
Email
lucyna.mastalerz@uj.edu.pl

12. IPD Sharing Statement

Learn more about this trial

Long-term Aspirin Therapy as a Predictor of Decreased Susceptibility to SARS-CoV-2 Infection in Aspirin-Exacerbated Respiratory Disease

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