Clinical trial NCT03825757: Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)
Official title: Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Rhinosinusitis (Diagnosis)
Keywords: chronic rhinosinusitis with nasal polyps
Acetyl salicylic acid exacerbated respiratory disease
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Helsinki
First posted: 2019-01-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double-blinded controlled trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in endoscopic Nasal polyp score of both sides of the nasal cavity.
timeFrame: at -4 days vs. at 11 months post-randomization
Secondary outcomes:
measure: Change in Sinonasal outcome test 22 (SNOT22). Validated nose-specific quality of life questionnaire, 0-110 points.
timeFrame: at -4 days vs. at 11 months post-randomization
measure: Change in the Relative forced expiratory volume in 1 second (FEV1%) without bronchodilator.
timeFrame: at -1 month vs. at 11 months post-randomization
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Sanna Toppila-Salmi, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: