Efficacy of Intermittent Tiotropium in Early Childhood Wheezing

Study Overview
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Brief Summary
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This study evaluates the effect of intermittent tiotropium bromide and salbutamol as needed versus intermittent fluticasone propionate and salbutamol as needed, or solely, salbutamol as needed on episode-free days in infants and toddlers with recurrent episodes of wheeze and/or shortness of breath.

Detailed Description
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Up to 30% of all children suffer from episodic wheeze or shortness of breath, i.e. asthmatic bronchitis, during the first three years of life. The condition is usually induced by viral respiratory infections, and short-acting beta-agonists are recommended as a monotherapy for symptoms unless there are at least four physician-confirmed episodes of wheeze or shortness of breath, or three episodes plus asthma risk factors. There is a current need for new therapeutic agents to treat asthmatic bronchitis in young children. In viral-induced wheeze, increased parasympathetic nerve activity results in increased acethylcholine release from nerve endings. Tiotropium bromide, an inhaled anticholinergic agent, prevents the acetylcholine function and achieves mild bronchodilatation and decrease in mucus secretion from the submucosal glands. The aim of the study is to find out the effect of intermittent tiotropium bromide and salbutamol as needed versus intermittent fluticasone propionate and salbutamol as needed, or solely, salbutamol as needed on episode-free days in infants and toddlers with recurrent episodes of wheeze and/or shortness of breath. Episode-free days are defined as those days during which there are no symptoms of wheeze and/or shortness of breath, no unscheduled medical visits for wheeze and/or shortness of breath, and no use of rescue or supplementary controller medications.

Official Title
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Efficacy of Intermittent Tiotropium in Early Childhood Wheezing

Conditions
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Wheezy Bronchitis, Asthmatic Bronchitis, Wheezing, Obstruction Airway

Intervention / Treatment
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* Drug: Tiotropium Bromide
* Drug: Fluticasone Propionate
* Drug: Salbutamol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children at the age of 6 to 35 months. Two to four physician-confirmed episodes of wheeze and/or shortness of breath. Parents/legal representatives with sufficient written and spoken skills in Finnish language. Exclusion Criteria: Birth before 36th week of gestation. Suspected/diagnosed chronic parenchymal lung disease or a structural airway defect, or a history of thoracotomy with pulmonary resection. A history of congenital or acquired heart disease, including any unstable or life-threatening cardiac arrhythmia. Constipation with a need of regular medication, or a diagnosed/suspected structural defect in the gastrointestinal tract. A history of malignancy, or other significant chronic disorder, disease, or defect.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

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 |
| --- | --- |
| Experimental: Tiotropium Bromide & Salbutamol<br>Inhaled Tiotropium Bromide 5 µg once a day, beginning at the onset of an upper respiratory tract infection and continuing for 7 to 14 days as needed, and inhaled Salbutamol 0.2 mg 4 to 6 times a day as needed for wheeze and shortness of breath | Drug: Tiotropium Bromide<br>* Tiotropium Bromide 2.5 µg/dose inhaled aerosol<br>* Other names: Spiriva Respimat;Drug: Salbutamol<br>* Salbutamol 0.1 mg/dose inhaled aerosol<br>* Other names: Ventoline Evohaler;|
| Active Comparator: Fluticasone Propionate & Salbutamol<br>Inhaled Fluticasone Propionate 125 µg twice a day, beginning at the onset of an upper respiratory tract infection and continuing for 7 to 14 days as needed, and inhaled Salbutamol 0.2 mg 4 to 6 times a day as needed for wheeze and shortness of breath | Drug: Fluticasone Propionate<br>* Fluticasone Propionate 125 µg/dose inhaled aerosol<br>* Other names: Flixotide Evohaler;Drug: Salbutamol<br>* Salbutamol 0.1 mg/dose inhaled aerosol<br>* Other names: Ventoline Evohaler;|
| Active Comparator: Salbutamol<br>Inhaled Salbutamol 0.2 mg 4 to 6 times a day as needed for wheeze and shortness of breath | Drug: Salbutamol<br>* Salbutamol 0.1 mg/dose inhaled aerosol<br>* Other names: Ventoline Evohaler;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Episode-free days | Effect on the episode-free days defined as the days during which there are no symptoms of wheeze and/or shortness of breath, no unscheduled medical visits for wheeze and/or shortness of breath, and no use of rescue or supplementary controller medications. | Up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unscheduled physician visits | Effect on the number of unscheduled physician visits for episodes of wheeze and/or shortness of breath. | Up to 48 weeks | 
| Rescue medication | Effect on the need for bronchodilative medication. | Up to 48 weeks | 
| Adverse events | Occurrence of adverse events. | Up to 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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shortness of breath, wheeze