Aspirin-Exacerbated Respiratory Disease (AERD) in patients with Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) MedDRA version: 25.1 Level: LLT Classification code 10075084 Term: Aspirin-exacerbated respiratory disease System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Aspegic 500 mg - Powder for oral solution
Pharmaceutical Form: Powder for oral solution in sachet
INN or Proposed INN: D,L-Lysine Acetylsalicylate
CAS Number: 62952-06-1
Other descriptive
Sponsors
UZ Leuven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients older than 18 years and younger than 75 years. - Patients with CRSwNP: (1) Presence of two or more symptoms for 12 weeks, one of which should be either nasal blockage/ obstruction/ congestion or nasal discharge (anterior/ posterior nasal drip) AND (2) Endoscopic signs of nasal polyps (bilateral) or history of revision sinus surgery in the treatment of bilateral nasal polyps. - Control cases: Patients with allergic rhinitis (AR): Presence of two or more symptoms for > 1 hour on most days: watery anterior rhinorrhoea /sneezing, especially paroxysmal/ nasal obstruction /nasal pruritis. AR must be confirmed by IgE test in blood and/or on skin. - Control cases: healthy volunteers: participants without clinical or radiographic history of sinus disease and with no known typical coexisting type 2 inflammatory diseases of nasal polyp disease, defined as asthma, allergic rhinitis, atopic dermatitis/eczema, urticaria, food allergy or eosinophilic esophagitis (based on anamnesis). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 176 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: - Participant has a history of anaphylaxis or of urticaria/angioedema to aspirin/NSAID. Participant had a reaction to aspirin/NSAID occurring within 10 minutes as this is likely to be IgE-mediated. - Female who is pregnant, breast-feeding or is of child-bearing potential and not using an adequate, highly effective contraceptive. - Participants with chronic urticaria, unstable cardiovascular conditions or severe or unstable/brittle asthma (FEV1 24 hours) for treatment of asthma within 3 months before screening. - Initiation of allergen immunotherapy within 3 months prior to screening or a plan to begin therapy or change its dose during the screening period. - Participants with major anatomical nasal abnormalities or conditions/concomitant diseases being responsible for nasal obstruction and making them nonevaluable at screening or for the nasal provocation test including, but not limited to: antrochoanal polyps, nasal septal deviation that would occlude at least one nostril, acute sinusitis, nasal infection or upper respiratory infection within 4 weeks prior to the test requiring treatment with systemic antibiotics, antivirals or antifungals. - Participants not willing to respect the wash-out period or not willing to take the necessary precautions in preparation to the challenge test as defined in section 5.3 ‘Concomitant/Prohibited Medication/Treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This clinical trial aims to determine the diagnostic performance and safety of nasal LAS provocation testing in the ENT department of a Belgian hospital to diagnose AERD in CRSwNP patients. Therefore, the trial has the following objectives: Primary objectives: (1) To determine the diagnostic performance by assessing the degree of agreement between history taking and the nasal provocation test for the diagnosis of AERD within CRSwNP patients and within different subgroups of CRSwNP patients defined by the severity of their condition (NPS, SNOT-22, ACQ-6, VAS, FEV1, PNIF) (2) To evaluate the safety of the procedure in terms of: (a) use of rescue medication other than nasal decongestants and short-acting beta2-agonists; (b) unplanned health care resource utilization; (c) allergic reactions not resolved after an observation period of 2 hours. ;Secondary Objective: Secondary objectives: Optimizing the procedure: To evaluate the step doses: if the percentage of participants with positive reactions on a certain provocative dose is strongly higher and the gap between the previous dose too much, than a lower dose could had been given with more safety for the patient Exploratory objectives: (1) To assess the effect of LAS on bronchial and nasal inflammation, (2) To assess the effect of LAS on exploratory biomarkers of inflammation, (3) To investigate biomarkers for predicting response to LAS, (4) To identify differences in upper airway inflammatory signature between CRSwNP and AERD, (5) To determine whether endotypic subtypes of AERD may exist. Furthermore, this trial will precede a main trial in which the capability of nasal ATAD to ameliorate AERD in CRSwNP will be tested. Therefore, the challenge test will serve as first step towards desensitization for the patients who tested positive. ;Primary end point(s): Diagnostic performance: - The proportion of patients scoring positive for AERD according to the challenge test - The proportion of patients scoring p | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Optimizing the procedure: - Incidence of positive reactions on the nasal provocation test per provocative dose Exploratory: - Change from baseline in the concentration of exhaled and nasal NO - Change from baseline in biomarkers of inflammation (cytokines representative of type 1, 2 and 3 inflammation and arachidonic acid derived lipid mediators) in nasal secretion and mucous membrane ;Timepoint(s) of evaluation of this end point: At the end of the trial | — |
Countries
Belgium
Contacts
Public ContactOtorhinolaryngology, head and neck
UZ Leuven
Outcome results
None listed