Trial Outcomes & Findings for Efficacy of Intermittent Tiotropium in Early Childhood Wheezing (NCT NCT03199976)
NCT ID: NCT03199976
Last Updated: 2024-09-19
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
80 participants
Primary outcome timeframe
Up to 48 weeks
Results posted on
2024-09-19
Participant Flow
Participant milestones
| Measure |
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
|
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
|
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
|
|---|---|---|---|
|
Overall Study
STARTED
|
27
|
25
|
28
|
|
Overall Study
COMPLETED
|
23
|
18
|
14
|
|
Overall Study
NOT COMPLETED
|
4
|
7
|
14
|
Reasons for withdrawal
| Measure |
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
|
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
|
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
|
|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
3
|
6
|
13
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
1
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Tiotropium Bromide & Salbutamol
n=27 Participants
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
|
Fluticasone Propionate & Salbutamol
n=25 Participants
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
|
Salbutamol
n=28 Participants
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
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
21.4 months
STANDARD_DEVIATION 7.0 • n=27 Participants
|
20.0 months
STANDARD_DEVIATION 6.8 • n=25 Participants
|
22.1 months
STANDARD_DEVIATION 6.0 • n=28 Participants
|
21.2 months
STANDARD_DEVIATION 6.6 • n=80 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=27 Participants
|
9 Participants
n=25 Participants
|
10 Participants
n=28 Participants
|
28 Participants
n=80 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=27 Participants
|
16 Participants
n=25 Participants
|
18 Participants
n=28 Participants
|
52 Participants
n=80 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Finland
|
27 Participants
n=27 Participants
|
25 Participants
n=25 Participants
|
28 Participants
n=28 Participants
|
80 Participants
n=80 Participants
|
PRIMARY outcome
Timeframe: Up to 48 weeksPopulation: Only those children with diary data available were included in the analysis.
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.
Outcome measures
| Measure |
Tiotropium Bromide & Salbutamol
n=26 Participants
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
|
Fluticasone Propionate & Salbutamol
n=25 Participants
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
|
Salbutamol
n=26 Participants
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
|
|---|---|---|---|
|
Percentage of Episode-Free Days
|
97 percentage of episode-free days
Interval 93.0 to 99.0
|
87 percentage of episode-free days
Interval 78.0 to 93.0
|
88 percentage of episode-free days
Interval 79.0 to 95.0
|
SECONDARY outcome
Timeframe: Up to 48 weeksEffect on the number of unscheduled physician visits for episodes of wheeze and/or shortness of breath.
Outcome measures
| Measure |
Tiotropium Bromide & Salbutamol
n=27 Participants
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
|
Fluticasone Propionate & Salbutamol
n=25 Participants
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
|
Salbutamol
n=28 Participants
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
|
|---|---|---|---|
|
Number of Participants With Unscheduled Physician Visits
|
10 Participants
|
10 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: Up to 48 weeksPopulation: Only patients with diary data available were included in the analysis.
Effect of the treatment on the need for bronchochilative and/or supplementary controller medication.
Outcome measures
| Measure |
Tiotropium Bromide & Salbutamol
n=26 Participants
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
|
Fluticasone Propionate & Salbutamol
n=25 Participants
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
|
Salbutamol
n=26 Participants
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
|
|---|---|---|---|
|
Percentage of Days Participants Needed Rescue Medication
|
2 percentage of days
Interval 0.0 to 7.0
|
13 percentage of days
Interval 6.0 to 21.0
|
12 percentage of days
Interval 6.0 to 20.0
|
SECONDARY outcome
Timeframe: Up to 48 weeksOccurrence of adverse events in treatment groups.
Outcome measures
| Measure |
Tiotropium Bromide & Salbutamol
n=27 Participants
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
|
Fluticasone Propionate & Salbutamol
n=25 Participants
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
|
Salbutamol
n=28 Participants
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
|
|---|---|---|---|
|
Number of Participants With Adverse Events
|
23 Participants
|
25 Participants
|
26 Participants
|
Adverse Events
Tiotropium Bromide & Salbutamol
Serious events: 4 serious events
Other events: 19 other events
Deaths: 0 deaths
Fluticasone Propionate & Salbutamol
Serious events: 3 serious events
Other events: 22 other events
Deaths: 0 deaths
Salbutamol
Serious events: 3 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tiotropium Bromide & Salbutamol
n=27 participants at risk
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
|
Fluticasone Propionate & Salbutamol
n=25 participants at risk
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
|
Salbutamol
n=28 participants at risk
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
|
|---|---|---|---|
|
Infections and infestations
Wheezy bronchitis and pneumonia
|
0.00%
0/27 • 48 weeks
|
0.00%
0/25 • 48 weeks
|
3.6%
1/28 • 48 weeks
|
|
Infections and infestations
Wheezy bronchitis and laryngitis
|
0.00%
0/27 • 48 weeks
|
4.0%
1/25 • 48 weeks
|
0.00%
0/28 • 48 weeks
|
|
Infections and infestations
Wheezy bronchitis and anaphylaxis to cashew
|
0.00%
0/27 • 48 weeks
|
4.0%
1/25 • 48 weeks
|
0.00%
0/28 • 48 weeks
|
|
Infections and infestations
Wheezy bronchitis
|
11.1%
3/27 • 48 weeks
|
4.0%
1/25 • 48 weeks
|
3.6%
1/28 • 48 weeks
|
|
Infections and infestations
Pneumonia
|
3.7%
1/27 • 48 weeks
|
0.00%
0/25 • 48 weeks
|
0.00%
0/28 • 48 weeks
|
|
Infections and infestations
Enteritis
|
0.00%
0/27 • 48 weeks
|
0.00%
0/25 • 48 weeks
|
3.6%
1/28 • 48 weeks
|
Other adverse events
| Measure |
Tiotropium Bromide & Salbutamol
n=27 participants at risk
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
|
Fluticasone Propionate & Salbutamol
n=25 participants at risk
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
|
Salbutamol
n=28 participants at risk
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
|
|---|---|---|---|
|
Infections and infestations
Otitis media
|
59.3%
16/27 • 48 weeks
|
36.0%
9/25 • 48 weeks
|
42.9%
12/28 • 48 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
48.1%
13/27 • 48 weeks
|
52.0%
13/25 • 48 weeks
|
32.1%
9/28 • 48 weeks
|
|
Infections and infestations
Wheezy bronchitis
|
25.9%
7/27 • 48 weeks
|
28.0%
7/25 • 48 weeks
|
42.9%
12/28 • 48 weeks
|
|
Infections and infestations
Conjunctivitis
|
14.8%
4/27 • 48 weeks
|
4.0%
1/25 • 48 weeks
|
25.0%
7/28 • 48 weeks
|
|
Infections and infestations
Enteritis
|
11.1%
3/27 • 48 weeks
|
12.0%
3/25 • 48 weeks
|
7.1%
2/28 • 48 weeks
|
|
Injury, poisoning and procedural complications
Minor trauma
|
7.4%
2/27 • 48 weeks
|
12.0%
3/25 • 48 weeks
|
7.1%
2/28 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
3.7%
1/27 • 48 weeks
|
12.0%
3/25 • 48 weeks
|
3.6%
1/28 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
Exanthema
|
3.7%
1/27 • 48 weeks
|
8.0%
2/25 • 48 weeks
|
7.1%
2/28 • 48 weeks
|
|
Infections and infestations
Tonsillitis
|
3.7%
1/27 • 48 weeks
|
4.0%
1/25 • 48 weeks
|
10.7%
3/28 • 48 weeks
|
|
Infections and infestations
Pharyngitis
|
7.4%
2/27 • 48 weeks
|
0.00%
0/25 • 48 weeks
|
7.1%
2/28 • 48 weeks
|
Additional Information
Dr Anne Kotaniemi-Syrjänen
Helsinki University Central Hospital
Phone: +35894711
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place