Asthmatic Bronchitis, Obstruction Airway, Wheezing, Wheezy Bronchitis
Conditions
Keywords
wheeze, shortness of breath
Brief summary
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
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 acetylcholine 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.
Interventions
DRUGTiotropium Bromide
Tiotropium Bromide 2.5 µg/dose inhaled aerosol
DRUGFluticasone Propionate
Fluticasone Propionate 125 µg/dose inhaled aerosol
DRUGSalbutamol
Salbutamol 0.1 mg/dose inhaled aerosol
Sponsors
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
No
Inclusion criteria
1. Children at the age of 6 to 35 months. 2. Two to four physician-confirmed episodes of wheeze and/or shortness of breath. 3. Parents/legal representatives with sufficient written and spoken skills in Finnish language.
Exclusion criteria
1. Birth before 36th week of gestation. 2. Suspected/diagnosed chronic parenchymal lung disease or a structural airway defect, or a history of thoracotomy with pulmonary resection. 3. A history of congenital or acquired heart disease, including any unstable or life-threatening cardiac arrhythmia. 4. Constipation with a need of regular medication, or a diagnosed/suspected structural defect in the gastrointestinal tract. 5. A history of malignancy, or other significant chronic disorder, disease, or defect.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Episode-Free Days | Up to 48 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Unscheduled Physician Visits | Up to 48 weeks | Effect on the number of unscheduled physician visits for episodes of wheeze and/or shortness of breath. |
| Percentage of Days Participants Needed Rescue Medication | Up to 48 weeks | Effect of the treatment on the need for bronchochilative and/or supplementary controller medication. |
| Number of Participants With Adverse Events | Up to 48 weeks | Occurrence of adverse events in treatment groups. |
Countries
Finland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium Bromide & Salbutamol 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
Tiotropium Bromide: Tiotropium Bromide 2.5 µg/dose inhaled aerosol
Salbutamol: Salbutamol 0.1 mg/dose inhaled aerosol | 27 |
| Fluticasone Propionate & Salbutamol 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
Fluticasone Propionate: Fluticasone Propionate 125 µg/dose inhaled aerosol
Salbutamol: Salbutamol 0.1 mg/dose inhaled aerosol | 25 |
| Salbutamol Inhaled Salbutamol 0.2 mg 4 to 6 times a day as needed for wheeze and shortness of breath
Salbutamol: Salbutamol 0.1 mg/dose inhaled aerosol | 28 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 3 | 6 | 13 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Fluticasone Propionate & Salbutamol | Salbutamol | Total | Tiotropium Bromide & Salbutamol |
|---|---|---|---|---|
| Age, Continuous | 20.0 months STANDARD_DEVIATION 6.8 | 22.1 months STANDARD_DEVIATION 6 | 21.2 months STANDARD_DEVIATION 6.6 | 21.4 months STANDARD_DEVIATION 7 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment Finland | 25 Participants | 28 Participants | 80 Participants | 27 Participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 28 Participants | 9 Participants |
| Sex: Female, Male Male | 16 Participants | 18 Participants | 52 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 25 | 0 / 28 |
| other Total, other adverse events | 19 / 27 | 22 / 25 | 23 / 28 |
| serious Total, serious adverse events | 4 / 27 | 3 / 25 | 3 / 28 |
Outcome results
Primary
Percentage of 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.
Time frame: Up to 48 weeks
Population: Only those children with diary data available were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tiotropium Bromide & Salbutamol | Percentage of Episode-Free Days | 97 percentage of episode-free days |
| Fluticasone Propionate & Salbutamol | Percentage of Episode-Free Days | 87 percentage of episode-free days |
| Salbutamol | Percentage of Episode-Free Days | 88 percentage of episode-free days |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Adverse Events
Occurrence of adverse events in treatment groups.
Time frame: Up to 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tiotropium Bromide & Salbutamol | Number of Participants With Adverse Events | 23 Participants |
| Fluticasone Propionate & Salbutamol | Number of Participants With Adverse Events | 25 Participants |
| Salbutamol | Number of Participants With Adverse Events | 26 Participants |
p-value: <0.05Chi-squared
Secondary
Number of Participants With Unscheduled Physician Visits
Effect on the number of unscheduled physician visits for episodes of wheeze and/or shortness of breath.
Time frame: Up to 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tiotropium Bromide & Salbutamol | Number of Participants With Unscheduled Physician Visits | 10 Participants |
| Fluticasone Propionate & Salbutamol | Number of Participants With Unscheduled Physician Visits | 10 Participants |
| Salbutamol | Number of Participants With Unscheduled Physician Visits | 14 Participants |
p-value: 0.595Chi-squared
Secondary
Percentage of Days Participants Needed Rescue Medication
Effect of the treatment on the need for bronchochilative and/or supplementary controller medication.
Time frame: Up to 48 weeks
Population: Only patients with diary data available were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tiotropium Bromide & Salbutamol | Percentage of Days Participants Needed Rescue Medication | 2 percentage of days |
| Fluticasone Propionate & Salbutamol | Percentage of Days Participants Needed Rescue Medication | 13 percentage of days |
| Salbutamol | Percentage of Days Participants Needed Rescue Medication | 12 percentage of days |
p-value: <0.01Wilcoxon (Mann-Whitney)