Efficacy and Safety of add-on Montelukast to Inhaled Budesonide in the Treatment of Nonasthmatic Eosinophilic Bronchitis

Study Overview
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Brief Summary
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Hypothesis: Add-on therapy with oral montelukast (Mon) to inhaled budesonide (BUD) may achieve better control of cough caused by nonasthmatic eosinophilic bronchitis (NAEB) with faster reduction of airway eosinophilia. Objective: To evaluate the efficacy of add-on therapy with Mon to inhaled corticosteroids (ICS) in the treatment of adult patients with chronic/subacute cough caused by NAEB diagnosed in outpatient setting. Primary endpoint：cough severity rated as cough visual analogue score (VAS)1 and eosinophil count in induced sputum during 4-week BUD monotherapy or Mon adjunct therapy.

Detailed Description
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Subjects：63 newly-diagnosed, steroid-naïve adult patients with chronic or subacute cough caused by NAEB. Grouping：ICS monotherapy (21 patients, BUD，400mcg mcg, twice daily+ placebo, 4 wks); Mon adjunct therapy (42 patients, Mon 10mg once daily + BUD 400mcg twice daily 4wks). Protocol Day 1: In the respiratory specialist clinic, the diagnosis of NAEB is established following the 2006 ACCP guideline (sputum eosinophilia >3%, negative chest radiography, spirometry and bronchial provocation test). After briefing, eligible subjects who have given informed written consents, are to be randomly allocated to different treatment groups. Patients' demographical data, course and nature of cough, accompanying symptoms and upper respiratory comorbidities, skin prick test to common aeroallergens1, baseline cough VAS (0-100 mm) 1, spirometry and induced sputum cell counts, will be recorded by the managing physician in case record file (CRF). Pulmicort Turbuhaler (AstraZeneca, budesonide 100 mcg/dose X 200 doses) will be prescribed to each patient. Day 2: Before initiation of treatment, at the Office for Clinical Trials, staff members will instruct the patients on correct usage of ICS, disperse Mon tablets or placebo as well as daily record cards, and explain how to record daily use of ICS and Mon, and adverse events. Once the treatment is initiated, oral steroids, other ICS, anti-histamines, beta-2 agonists and theophyllines will not be prescribed and used throughout the study period. Day 8、15：Revisits: Patients' nature of cough, accompanying symptoms, cough VAS, induced sputum cell count will be reevaluated and recorded in CRF. Old daily record cards will be collected. New ones as well as Mon tablets or placebo will be given. Patients' skill of using ICS, compliance, systemic or local adverse events will be monitored. Day 29： Revisit: Patients' nature of cough, accompanying symptoms, cough VAS, spirometry, bronchial provocation test, induced sputum cell count will be reevaluated and recorded in CRF. Old daily record cards will be collected. Patients' skill of using ICS, compliance, systemic or local adverse events will be recorded.

Official Title
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Randomized Double-blind Placebo-controlled Study of add-on Montelukast to Inhaled Budesonide in the Treatment of Nonasthmatic Eosinophilic Bronchitis

Conditions
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Nonasthmatic Eosinophilic Bronchitis

Intervention / Treatment
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* Drug: Montelukast
* Other: placebo to montelukast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult nonsmoking NAEB patients Without history of taking Mon, oral or inhaled corticosteroids, and Without bacterial or viral respiratory infections within 30 days prior to diagnosis of NAEB Exclusion Criteria: Current smokers Pregnant or lactating women Known allergy to Mon, oral or inhaled corticosteroids Unable to use ICS following repeated instructions Complicated with unresectable malignancy or severe heart, lung, liver or kidney diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: combination therapy<br>combination therapy with inhaled budesonide and oral montelukast | Drug: Montelukast<br>* 10mg, qn, 4 weeks<br>* Other names: Singulair;|
| Placebo Comparator: monotherapy<br>monotherapy with inhaled budesonide and placebo of montelukast | Other: placebo to montelukast<br>* same appearance, flavor, weight, and size to montelukast pills, 1 pill daily, for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cough severity rated as cough visual analogue score (VAS) |  | 4 weeks | 
| eosinophil count in induced sputum |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse reactions | any discomforts or untoward events observed during the study period | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAEB, chronic cough, montelukast, induced sputum