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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Rhinosinusitis (Diagnosis)
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Acetyl Salicylic Acid

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sanna Toppila-Salmi, MD PhD; Phone Number: +358505431421; Email: sanna.salmi@helsinki.fi
• Study Contact Backup: Name: Annina Lyly, MD PHD; Phone Number: +358505455051; Email: annina.lyly@hus.fi

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primaspan tablet 250 mg; 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; Primaspan 250 mg tablet Acetyl Salicylic Acid; Other Names: Primaspan 250 mg tablet
Placebo Comparator: Placebo tablet; 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; Placebo Oral Tablet; Other Names: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanna Salmi
• Collaborators: University of Helsinki
• Investigators: Principal Investigator: Sanna Toppila-Salmi, MD PhD, Helsinki University Central Hospital

Publications and helpful links

Helpful Links

• Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper.
• Aspirin-Exacerbated Respiratory Disease. Publication.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2019
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: January 26, 2019
• First Submitted That Met QC Criteria: January 30, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: chronic rhinosinusitis with nasal polyps; Acetyl salicylic acid exacerbated respiratory disease
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Dermatologic Agents; Antifungal Agents; Keratolytic Agents; Aspirin; Salicylic Acid; Salicylates
• Other Study ID Numbers: TYH2018203; 2017-001570-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data is owned by Helsinki University Hospital and University of Helsinki.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No