Wheezy BronchitisPhase 4NCT03199976
Efficacy of Intermittent Tiotropium in Early Childhood Wheezing
A Phase 4 study testing Tiotropium Bromide, Fluticasone Propionate and Salbutamol in people with Wheezy Bronchitis and Asthmatic Bronchitis, run by Helsinki University Central Hospital at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 35 months
- Conditions the study is for
- Wheezy Bronchitis, Asthmatic Bronchitis, Wheezing
- What is being tested?
- Tiotropium Bromide, Fluticasone Propionate and Salbutamol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteFinland
- Study dates
- 20 Apr 2016to 18 Nov 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 35 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Finland1 site
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland
Helsinki, FI-00029 HUS
About this study
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.
Read the 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.
- Conditions
- Wheezy Bronchitis, Asthmatic Bronchitis, Wheezing, Obstruction Airway
- Being tested
- Tiotropium Bromide, Fluticasone Propionate, Salbutamol
- Keywords
- wheeze, shortness of breath
- Medical subject headings
- Bronchiolitis, Respiratory Sounds, Airway Obstruction, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tiotropium BromideDrug
Also called Spiriva Respimat
Tiotropium Bromide 2.5 µg/dose inhaled aerosol
Fluticasone PropionateDrug
Also called Flixotide Evohaler
Fluticasone Propionate 125 µg/dose inhaled aerosol
SalbutamolDrug
Also called Ventoline Evohaler
Salbutamol 0.1 mg/dose inhaled aerosol
| Study group | Role | What they receive |
|---|---|---|
| Tiotropium Bromide & Salbutamol | Experimental | 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 Receives: Drug: Tiotropium Bromide; Drug: Salbutamol |
| Fluticasone Propionate & Salbutamol | Active comparator | 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 Receives: Drug: Fluticasone Propionate; Drug: Salbutamol |
| Salbutamol | Active comparator | Inhaled Salbutamol 0.2 mg 4 to 6 times a day as needed for wheeze and shortness of breath Receives: Drug: Salbutamol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 48 weeks
Secondary outcomes (3)
Number of Participants With Unscheduled Physician Visits
Effect on the number of unscheduled physician visits for episodes of wheeze and/or shortness of breath.
Measured: Up to 48 weeks
Percentage of Days Participants Needed Rescue Medication
Effect of the treatment on the need for bronchochilative and/or supplementary controller medication.
Measured: Up to 48 weeks
Number of Participants With Adverse Events
Occurrence of adverse events in treatment groups.
Measured: Up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2017
- Study start20 Apr 2016
- Primary completion18 Nov 2020
- Study completion18 Nov 2020
Why it stopped: Subjects in the Salbutamol group discontinued the intervention more often due to troublesome respiratory symptoms
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Wheezy BronchitisStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anne Kotaniemi-Syrjänen, Helsinki University Central Hospital
- Investigators
- Mika J Mäkelä, Professor, Study director, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199976
- Sponsor's protocol ID
- TFS01
- Other IDs
- 2015-002985-22, 2015
- Status last verified
- May 2024
- First submitted
- 26 Jun 2017
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Deidentified individual participant data will not be made available.
Publications
Kotaniemi-Syrjanen A, Klemola T, Koponen P, Jauhola O, Aito H, Malmstrom K, Malmberg LP, Rahiala E, Sarna S, Pelkonen AS, Makela MJ. Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial. Pediatrics. 2022 Sep 1;150(3):e2021055860. doi: 10.1542/peds.2021-055860.
PubMed 35942814
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Intermittent Tiotropium in Early Childhood Wheezing
- ClinicalTrials.gov ID
- NCT03199976
- Acronym / sponsor ID
- TFS01
- Conditions
- Wheezy Bronchitis, Asthmatic Bronchitis, Wheezing, Obstruction Airway
- Keywords
- wheeze, shortness of breath
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Subjects in the Salbutamol group discontinued the intervention more often due to troublesome respiratory symptoms
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Study start
- 20 Apr 2016 (actual)
- Primary completion
- 18 Nov 2020 (actual)
- Study completion
- 18 Nov 2020 (actual)
- First posted
- 27 Jun 2017 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tiotropium Bromide & Salbutamol | Experimental | Drug: Tiotropium Bromide, Drug: SalbutamolInhaled 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 |
| Fluticasone Propionate & Salbutamol | Active comparator | Drug: Fluticasone Propionate, Drug: SalbutamolInhaled 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 |
| Salbutamol | Active comparator | Drug: SalbutamolInhaled Salbutamol 0.2 mg 4 to 6 times a day as needed for wheeze and shortness of breath |
Who may qualify
- Ages
- 6 to 35 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tiotropium BromideAlso: Spiriva RespimatTiotropium Bromide 2.5 µg/dose inhaled aerosol | Drug | Tiotropium Bromide & Salbutamol |
| Fluticasone PropionateAlso: Flixotide EvohalerFluticasone Propionate 125 µg/dose inhaled aerosol | Drug | Fluticasone Propionate & Salbutamol |
| SalbutamolAlso: Ventoline EvohalerSalbutamol 0.1 mg/dose inhaled aerosol | Drug | Fluticasone Propionate & Salbutamol, Salbutamol, Tiotropium Bromide & Salbutamol |
Primary outcome
Percentage of Episode-Free Days
Time frame: 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.
3 secondary outcomes
Number of Participants With Unscheduled Physician Visits
Time frame: Up to 48 weeks
Percentage of Days Participants Needed Rescue Medication
Time frame: Up to 48 weeks
Number of Participants With Adverse Events
Time frame: Up to 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35942814Kotaniemi-Syrjanen A, Klemola T, Koponen P, Jauhola O, Aito H, Malmstrom K, Malmberg LP, Rahiala E, Sarna S, Pelkonen AS, Makela MJ. Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial. Pediatrics. 2022 Sep 1;150(3):e2021055860. doi: 10.1542/peds.2021-055860.
- Individual participant dataSharing planned: No. Deidentified individual participant data will not be made available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mika J Mäkelä, Professor study director
Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tiotropium Bromide, Fluticasone Propionate and Salbutamol in people with Wheezy Bronchitis and Asthmatic Bronchitis, run by Helsinki University Central Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Episode-Free Days (time frame: Up to 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03199976, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.