Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)

Study Overview
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Brief Summary
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The study is performed as a randomized double-blinded prospective controlled trial. A total of 72 adult Acetyl salicylic acid (ASA) -exacerbated respiratory disease (AERD) -patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) will be recruited. Those negative to ASA-challenge test will not enter the Clinical Trial . All patients entering the Clinical Trial, have undergone earlier ethmoidal surgery (partial/total) and have not gained disease control. F-helicobacter antigen is tested and treatment is given if indicated. The patients are recruited at the Helsinki University Hospital (HUH). The study will be monitored by a professional monitor. Electronic CRF and paper/electronic patient questionnaires provided by HUS will be used (eCRF and patient questionnairea, Granitics).

Detailed Description
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Randomization and the treatment arms I-II: The patients are randomized to two treatment arms I) ASA- desensitization po tablet daily for 11 months (n=36) II) Placebo po tablet daily for 11 months (n=18). ASA challenge and desensitization (Primaspan) /Placebo: is conducted according to modified international protocol. FEV1 should be at least 1.5 L and > 60% of predicted before challenge or desensitization. On the first day every patient will receive 25 mg + 25 mg ASA at a hospital setting. On the second day every patient will receive 50 mg + 25 mg ASA at a hospital setting. On the third day every patient will receive 75 mg + 25 mg ASA at a hospital setting. On the fourth day every patient will receive 100 mg + 25 mg ASA at a hospital setting. During the ASA challenge, patient who is ASA-challenge positive is then randomized and starts the trial so that he/she uses blinded ½ tablet of 250 mg ASA or ½ tablet of placebo daily at home for the next 1 month. After this period of 1 month, the dosing is increased at hospital setting, so that the patient receives blindly 250 mg ASA 1/2 tablet + 1/2 tablet or placebo 1/2 tablet + 1/2 tablet. Thereafter he/she will continue using blindly 250 mg ASA 1 tablet or placebo 1 tablet daily at home for the next 10 months. If the patient does not tolerate the up-dosing of ASA/placebo, he/she will continue using blindly ½ tablet of 250 mg ASA/placebo daily at home for the next 10 months. The total duration of the ASA/placebo treatment is 11 months. We additionally take nasal, blood and urine samples during the trial. Follow-ups. The symptom questionnaire and interview of side-effects are performed during each visit. Lung function (eNO, nNO, PEF, spirometry) is monitored and the patient will visit doctor and/or nurse at 1, 5, 11, and 12 months post-starting with the treatment. Samples are taken during recruitment visit, before and after ASA-challenge and at 5, 11 and 12 months post-starting with the treatment. We also monitor side-effects, exacerbations, need of medication (po. cortisocteroids; antibiotics) and satisfaction to treatment. Primary end point is change in nasal endoscopic nasal polyp score at -4 days vs. +11 months post-randomization. Secondary end point is change in Sinonasal Outcome Test -22 (SNOT-22) score at -4 days vs. +11 months post-randomization, and change in relative Forced expiratory volume in 1 second (FEV1 %) without bronchodilator at -1 month vs. +11 months post-randomization. Safety (complications, adverse effects), costs and loss of productivity between study arms will be compared. Trial medication will be discontinued, if surgery is needed before the end of follow-up.

Official Title
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Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)

Conditions
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Chronic Rhinosinusitis (Diagnosis)

Intervention / Treatment
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* Drug: Placebo Oral Tablet
* Drug: Acetyl Salicylic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ALL these need to be positive: Endoscopic nasal polyp score ≥4 SNOT-22 ≥30 Sinus Computed tomography Lund-Mackay score ≥14. The new sinus CT scans are needed if the previous sinus CT scans have been performed over 36 months before recruitment visit or if there is a suspicion of complication of CRS (f.ex. mucocele, invasive fungal rhinosinusitis) ≥1 previous partial/total ethmoidectomy surgery. In addition, patient should have a history of at least one of the following: >1 oral corticosteroids during the past two years >3 antibiotic courses during the past two years. In patients with contraindication/adverse effects in using oral steroids additional criteria are not required. Exclusion Criteria: complication of CRS (f.e. mucocele, invasive fungal rhinosinusitis) bleeding diathesis pregnancy/ breastfeeding cystic fibrosis primary ciliary dyskinesia (PCD) sarcoidosis granulomatosis with polyangitis (GPA) eosinophilic granulomatosis with polyangitis (EGPA) immunosuppression (diagnosed Spesific antibody deficiency (SAD), CVI, HIV use of biologicals/immunosuppressive medication immunotherapy Daily use of systemic corticosteroids (Prednisolon 10mg or equivalent) -communication problems (f.e. neurological/psychiatric disease, language skills) -unlikely to comply other severe disease uncontrolled asthma ASA-challenge negative gastric ulcer anticoagulant treatment SSRI-depression medication beta-blocker severe chronic urticaria ASA anaphylaxis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blinded controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primaspan tablet 250 mg<br>Primaspan tablet 250 mg (Acetyl salicylic acid): 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day. | Drug: Acetyl Salicylic Acid<br>* Primaspan 250 mg tablet Acetyl Salicylic Acid<br>* Other names: Primaspan 250 mg tablet;|
| Placebo Comparator: Placebo tablet<br>Placebo Oral Tablet: 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day. | Drug: Placebo Oral Tablet<br>* Placebo Oral Tablet<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in endoscopic Nasal polyp score of both sides of the nasal cavity. | Change means differences between at time -4 days versus (vs.) at time +11 months post-randomization. Minimum value is 0. Maximum value is 8. A higher score means worse outcome. | at -4 days vs. at 11 months post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sinonasal outcome test 22 (SNOT22). Validated nose-specific quality of life questionnaire, 0-110 points. | Change means differences between at time -4 days vs. +11 months post-randomization. A higher score means worse outcome. | at -4 days vs. at 11 months post-randomization | 
| Change in the Relative forced expiratory volume in 1 second (FEV1%) without bronchodilator. | Change means differences between at time -1 month vs. +11 months post-randomization. A higher value means better outcome. FEV1% is measured by Spirometry. | at -1 month vs. at 11 months post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic rhinosinusitis with nasal polyps, Acetyl salicylic acid exacerbated respiratory disease