The Efficacy of Budesonide/Formoterol in Cough Variant Asthma

Study Overview
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Brief Summary
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Cough variant asthma (CVA), subtype of bronchial asthma, is considered to be one of the most common causes of chronic cough in different cough guidelines of United States, Europe, China and other countries. From a multicenter survey in China, over one third of chronic cough is caused by CVA, which is higher than western countries. CVA differs from classic asthma, usually manifesting a symptom of only coughing without wheezing or dyspnea and particularly coughing at night. With less clinical manifestation and medical intervention, CVA patients are easily be neglected and misdiagnosed, and 30-40% of them will develop to typical asthma in the next few years. Currently there's no specific therapy recommendation for CVA in GINA. Although cough guidelines in China recommend that CVA patients should be treated as typical asthma, no recommendation on details about ICS/LABA dosage and duration. There are only a few sporadic CVA therapy researches with small sample size. Two studiesfound that CVA patients can't get cough symptom relief even after treating by low dose of ICS/LABA for 3 months. Some patients' cough symptom relapses during the 24-week follow-up phase after treating by ICS/LABA for 3 months. Overall, the best treatment of CVA is not yet clear. GINA 2018 emphasize that asthma need long-term management. Euro-SMART study found that budesonide/formoterol 2 inhalation twice daily plus as needed can reduce daytime asthma symptoms and night-time awakenings, as well as reduce exacerbation risk more than 1 inhalation twice daily. Based on the above reasons, We assume that increase the dosage of ICS/LABA can decrease relapse rate in CVA patients with severe cough. This multi-center, randomized, controlled clinical trial can help to clarify the best dosage of budesonide/formoterol of CVA in China.

Official Title
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The Efficacy of Budesonide/Formoterol in Cough Variant Asthma -- A Multi-center Randomized, Controlled Clinical Trial

Conditions
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Cough Variant Asthma

Intervention / Treatment
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* Drug: budesonide/formoterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients, with age ≥18，≤70 years old. Diagnose with CVA CSS(cough symptom score, daytime + nighttime) ≥ 3 points Exclusion Criteria: Participated in any interventional clinical trial during the last 90 days. Pregnancy Associated with a clear history of other lung diseases, or combined with other systems severe illness. A abuse history of alcohol or narcotic drug, or have a mental history, confrontation personality, adverse motives, suspicious or other emotional or intellectual problems that may affect the informed validity of the study With a history of upper respiratory tract infection acute exacerbation within 4 weeks before enrolment. Clinical abnormalities associated with symptoms in chest radiology. Smokers On medications of ACEI or ARB Not suitable for study observation judged by investigators

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Controlled group<br>Controlled group: budesonide/formoterol(SYM) 160/4.5ug 1 inhalation bid* 3 months (n=250). | Drug: budesonide/formoterol<br>* apply different dosage of budesonide/formoterol in two groups and evaluate the treatment effects.<br>|
| Experimental: Study group<br>Study group: SYM 160/4.5ug 2 inhalation bid* 3 months (n=250). | Drug: budesonide/formoterol<br>* apply different dosage of budesonide/formoterol in two groups and evaluate the treatment effects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of CVA patient with symptom relapse | Relapse rate during the 6-months' follow-up phase after treating by different doses of budesonide/formoterol for 3 months. | during 6-months' follow-up phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of CVA patient with symptom relief | symptom relief rate after treating by different doses of budesonide/formoterol for 3 months. | after treating by different doses of budesonide/formoterol for 3 months. |