Study design: multicenter, national, non-interventional, prospective study evaluating the
effectiveness of Trimbow 172/5/9 μg pMDI on symptom scores in 6 months after switch from
previous LABA-high dose ICS or LABA-high dose ICS + LAMA containing treatment in
asthmatic patients.
Dosage regimen and administration Name of the product: Trimbow 172/5/9 micrograms
pressurised inhalation, solution. Each delivered dose (the dose leaving the mouthpiece)
contains 172 μg of beclometasone dipropionate, 5 μg of formoterol fumarate dihydrate and
9 μg of glycopyrronium (as 11 μg glycopyrronium bromide). Each metered dose (the dose
leaving the valve) contains 200 μg of beclometasone dipropionate, 6 μg of formoterol
fumarate dihydrate and 10 μg of glycopyrronium (as 12.5 μg glycopyrronium bromide). The
recommended dose is two inhalations twice daily. The maximum dose is two inhalations
twice daily.
Aim of the study (research objective)
Primary objective:
The main objective is to assess the effectiveness of BDP/FF/G 172/5/9 μg fixed
triple combination in a real-world setting, with regards to improvements in symptom
scores (ACT - Asthma Control Test).
Primary outcome measures:
Change (improvement) of ACT score, during the 6 months of treatment (Visit 3),
compared to the score at baseline.
The percentage of patients achieving an improvement in ACT score of 3 points
(MCID, minimum clinically important difference) or more, after the 6-month
treatment (Visit 3) compared to baseline.
Secondary objectives:
Secondary objectives are the assessments of improvement in lung function, adherence
to treatment, and health-related quality of life.
Test sample and method, recruitment principle No patient recruitment will be
performed. Eligible patients will be enrolled during the participating physicians'
regular asthma patient management and patients' written informed consent. Patient
inclusion will take place among patients having severe asthma at outpatient clinics
(the chosen study sites are attached as annexes to the study protocol), strictly at
the time of the patients' visit. The planned number of patients is up to 300.
Structure of the study In accordance with the requirements of non-interventional
studies, the assignment of patients to Trimbow 172/5/9 μg pMDI therapy should be
made independently of the study. Patient enrolment can take place after the patient
has been fully informed about the purpose of the study and all its details, and the
patient has read and signed the patient informed consent form, including any
questions they may have. Once this has taken place, the data that would have been
generated anyway during the outpatient examination of the patient in accordance with
daily practice can be recorded. This is considered the first visit of the study
(Visit 1). During this visit, the patient's main demographic data, information on
comorbidities and concomitant medications, smoking history, previous and current
asthma therapies, asthma specific assessment (including ACT), exacerbation history,
post-dose lung function values, maintenance and reliever inhaled therapies (former
and new) baseline quality of life based on the asthma quality of life (EQ-5D-5L)
questionnaire, and adherence to therapy based on Test of Adherence to Inhalers
(TAI-12) questionnaire are recorded (data to be recorded in e-CRF). Patients will
then attend two additional visits - Visit 2 - 1 month (30 ± 5 days) and Visit 3 - 6
months ± 10 days after enrolment as per routine clinical practice. During these
visits, data will be collected, according to routine clinical practice. If the
patient's maintenance therapy changes during the study as decided by the treating
physician, and the patient is no longer receiving Trimbow 172/5/9 μg pMDI, the
patient will be automatically excluded from this NIS. The therapy modification and
its exact date must be recorded in the eCRF (electronic Case Report Form) of the
next visit. If the change in therapy is related to a suspected adverse reaction, it
should be reported separately in the eCRF platform in accordance with the respective
section of the protocol.
This NIS is open to all eligible patients according to the inclusion and exclusion
criteria. Permitted concomitant treatments: allowed all medications according to
local clinical practice (any non-inhalation therapy for asthma or other diseases)
and reliever (short-acting bronchodilators) inhaled therapies for asthma.
Start and duration of the study The enrolment of the patients can start only after
the approval of the Bulgarian Drug Agency and Ethics Committee for Clinical Trials.
The study is planned to start at the end of January 2025. Each site will have 3
months to enroll patients. Following the completion of patient enrolment, each
patient will be followed up for 6 months. After the visit of the last patient, sites
will have one month to collect all missing data/correct any data flagged as
erroneous during monitoring. The last patient last visit is expected to take place
in October/November 2025, and the study is planned to be concluded in March/April
Secondary objectives are the assessments of improvement in lung function, adherence
to treatment, and health-related quality of life.

2. Test sample and method, recruitment principle No patient recruitment will be
performed. Eligible patients will be enrolled during the participating physicians'
regular asthma patient management and patients' written informed consent. Patient
inclusion will take place among patients having severe asthma at outpatient clinics
(the chosen study sites are attached as annexes to the study protocol), strictly at
the time of the patients' visit. The planned number of patients is up to 300.

3. Structure of the study In accordance with the requirements of non-interventional
studies, the assignment of patients to Trimbow 172/5/9 μg pMDI therapy should be
made independently of the study. Patient enrolment can take place after the patient
has been fully informed about the purpose of the study and all its details, and the
patient has read and signed the patient informed consent form, including any
questions they may have. Once this has taken place, the data that would have been
generated anyway during the outpatient examination of the patient in accordance with
daily practice can be recorded. This is considered the first visit of the study
(Visit 1). During this visit, the patient's main demographic data, information on
comorbidities and concomitant medications, smoking history, previous and current
asthma therapies, asthma specific assessment (including ACT), exacerbation history,
post-dose lung function values, maintenance and reliever inhaled therapies (former
and new) baseline quality of life based on the asthma quality of life (EQ-5D-5L)
questionnaire, and adherence to therapy based on Test of Adherence to Inhalers
(TAI-12) questionnaire are recorded (data to be recorded in e-CRF). Patients will
then attend two additional visits - Visit 2 - 1 month (30 ± 5 days) and Visit 3 - 6
months ± 10 days after enrolment as per routine clinical practice. During these
visits, data will be collected, according to routine clinical practice. If the
patient's maintenance therapy changes during the study as decided by the treating
physician, and the patient is no longer receiving Trimbow 172/5/9 μg pMDI, the
patient will be automatically excluded from this NIS. The therapy modification and
its exact date must be recorded in the eCRF (electronic Case Report Form) of the
next visit. If the change in therapy is related to a suspected adverse reaction, it
should be reported separately in the eCRF platform in accordance with the respective
section of the protocol.

This NIS is open to all eligible patients according to the inclusion and exclusion
criteria. Permitted concomitant treatments: allowed all medications according to
local clinical practice (any non-inhalation therapy for asthma or other diseases)
and reliever (short-acting bronchodilators) inhaled therapies for asthma.

4. Start and duration of the study The enrolment of the patients can start only after
the approval of the Bulgarian Drug Agency and Ethics Committee for Clinical Trials.
The study is planned to start at the end of January 2025. Each site will have 3
months to enroll patients. Following the completion of patient enrolment, each
patient will be followed up for 6 months. After the visit of the last patient, sites
will have one month to collect all missing data/correct any data flagged as
erroneous during monitoring. The last patient last visit is expected to take place
in October/November 2025, and the study is planned to be concluded in March/April
2026.

5. Study plan A total of 3 visits will be performed for the assessment of the primary
and secondary endpoints during the study. Patients may be enrolled in the study and
their data may be recorded, only if this data is recorded in accordance with
standard medical practice.
- Visit 1: time of enrolment - a normal visit, according to routine clinical
practice. Informed consent and baseline patient characteristics will be
collected.
- Visit 2: 1 month after enrolment (30 days ± 5 days after Visit 1)
- Visit 3: 6 months after enrolment (± 10 days).