Periostin-guided Withdrawal of Inhaled Corticosteroids in Patients With Non-eosinophilic Asthma

Study Overview
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Brief Summary
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Background: Asthma is a common chronic condition characterized by respiratory symptoms and hyperresponsive airways. According to treatment guidelines, patients with persistent asthma require daily treatment with inhaled corticosteroids (ICS). However, certain subgroups of asthma patients such as non-eosinophilic asthma patients do not respond well to the ICS treatment. In the present study, asthma patients treated with ICS and exhibiting low levels of eosinophilic biomarkers such as S-periostin, FeNO and blood eosinophils, are randomized 1:1 to either 1) tapering of ICS or 2) usual care. Thus, the aim of the present study is to investigate whether patients with non-eosinophilic asthma can sustain their level of disease control during ICS tapering. Design: This is a randomized, controlled, one-center, non-inferiority study of ICS tapering in patients with non-eosinophilic asthma. Inclusion and exclusion criteria: 1) Objectively secured asthma diagnosis, 2) Age 18-65 years, 3) ICS treatment equivalent to Budesonide 800 microg daily or more with at least 80% adherence, 4) Serum-periostin < 50 ng/ml, 5) FeNO<25 ppb at all prior visits, 6) Blood-eosinophils<0.15 at screening, 7) no allergic asthma history, 8) no daily smoking within 6 months, 9) no other respiratory disease, 10) no daily treatment with immunosuppressives, 11) no pregnancy, and 12) no history of drug or alcohol abuse. Endpoints: Primary: Change in Control Questionnaire (ACQ) from baseline to post-tapered ICS and time from baseline to drop-out. Secondary: Change in FeNO, change in Serum-Periostin, change in FEV1, change in blood-eosinophils. Methods: Relevant patients will be recruited from Respiratory Outpatient Wards. In total, 110 patients will be required. Visits will be performed at screening, at week 0, 4, 8, 12, 16, 26, 52. In the active arm, ICS dosage will be reduced to 50% at week 0 and removed at week 8. All visits include ACQ, FeNO, spirometry, blood eosinophils. S-periostin will be measured at screening and at week 8 and 16.

Official Title
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Periostin-guided Withdrawal of Inhaled Corticosteroids in Patients With Non-eosinophilic Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Tapering of inhaled corticosteroid (ICS) treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Astma patients followed in the Respiratory Outpatient Ward, Hvidovre Hospital, Amager Hospital or Glostrup Hospital. At least one of the following test suggestive for asthma, performed at any time during the outpatient course: 1) FEV1-reversibility on at least 12% and 200 ml after administration of bronchodilator or Prednisolon course, 2) positive bronchial provocation test, such as mannitol, 3) peakflow (PF)-variation of at least 20% assessed during a 14-day period, measured twice daily and at asthmatic symptoms, or 4) Variability in FEV1 on at least 12% and 200 ml Age 18-65 years Treated with ICS daily in doses equivalent to Budesonide 800 microg daily or more ICS adherence of at least 80% during the last year, assessed from used prescriptions Serum-periostin < 50 ng/ml at screening (8) FeNO < 25 ppb at all prior visits Blood-eosinophils <0,15 at screening Signed informed consent Exclusion Criteria: History of allergic asthma Doctor-diagnosed pneumonia within 6 weeks prior to screening Daily smoking or former daily smoking within the last 6 months Known other respiratory conditions such as COPD or pulmonary sarcoidosis Known other chronic conditions that could impact or prevent study participation, including severe heart conditions and conditions requiring treatment with immunosuppressive drugs such as Prednisolon, Methotrexate or biological treatments, assessed by study doctor Pregnancy or planned pregnancy Abuse of alcohol or other recreational drugs

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group A<br>Usual care. Unchanged asthma medication during the entire study period. | |
| Experimental: Group B<br>Tapering of ICS over 8 weeks. Dosis reduction of 50% in ICS treatment for 8 weeks, followed by total ICS removal. Other inhaled asthma medication remains unchanged during the entire study period. | Drug: Tapering of inhaled corticosteroid (ICS) treatment<br>* Tapering of ICS treatment over 8 weeks. Follow-up over 52 weeks in total. Dosis reduction of 50% in ICS treatment for 8 weeks, followed by total ICS removal. Other inhaled asthma medication remains unchanged during the entire study period.<br>* Other names: ciclesonide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Control Questionnaire (ACQ) from baseline to post-tapered ICS |  | 52 weeks | 
| Time from baseline to drop-out |  | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FeNO |  | 52 weeks | 
| Change in FEV1 |  | 52 weeks | 
| Change in blood eosinophils |  | 52 weeks | 
| Change in serum periostin |  | 52 weeks |