Fixed Triple Inhaled Combination in Asthmatic Patients in a Real-life Setting

Active, not recruiting

• Conditions: Asthma; Asthma Patients; Asthma Bronchiale
• Interventions: Drug: BDP/FF/G (Beclomethasone diprprionate, formoterol fumarate, glycopyrronium bromide) 172/5/9 μg

• Registration Number: NCT06786767
• Lead Sponsor: Chiesi Bulgaria

Brief Summary

The mainstay of asthma treatment are ICSs, mostly and usually combined with LABA. In the past decade LAMA had been accepted as an add-on treatment for patients on GINA treatment Steps 4 and 5. Recently, RCTs proved the efficacy and safety of fixed triple combinations of moderate and high dose of ICS and LABA, LAMA in a very selected asthmatic population, resulting in the market authorization of these products. However, there is a lack of evidence on the real-world effectiveness of these therapies, especially with regards to improvement in symptom scores and quality of life.

Detailed Description

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.

1. 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.

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).

Study Timeline

• Study First Submitted: 2025-01-16
• Study First Submitted QC: 2025-01-16
• Study First Posted: 2025-01-22
• Study Start: 2025-02-01
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-01
• Last Update Posted: 2025-08-06
• Primary Completion: 2026-01-15
• Study Completion: 2026-02-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 281

Inclusion Criteria

1. Physician-confirmed clinical diagnosis of asthma according to GINA guidelines and treated for at least 3 years before inclusion

2. Patients ≥ 18 years of age in ambulatory care

3. Patients who are eligible for the use of Trimbow 172/5/9 μg pMDI according to the SmPC

   1. patients who experienced one or more asthma exacerbation in the previous year AND
   2. patients not adequately controlled according to the physician's clinical assessment despite the use of b1) LABA and high dose ICS OR b2) LABA and high-dose ICS + LAMA multi-inhaler triple therapy. FEV1<80% at baseline. (spirometry performed at the visit 1 independently of the study or up to 30 days before the enrolment or within 3 days after Visit 1 is acceptable).

4. Inhaled asthma therapy was changed to Trimbow 172/5/9 μg pMDI no more than 2 weeks prior to OR on the day of study inclusion 6. Patient provided written, informed consent to study participation

Exclusion Criteria

1. Participation in any clinical trial within 30 days prior to enrolment
2. Patients hospitalized due to an exacerbation of their asthma within the last 4 weeks prior to enrolment.
3. Diagnosis of COPD.
4. Tuberculosis (active or anamnestic)
5. Actual or previous use of biologics for asthma treatment in the past 12 months
6. All exclusion criteria listed in Trimbow 172/5/9 μg pMDI SmPC
7. Hypersensitivity to the active substances or to any of the excipients listed in the SmPC
8. Pregnancy and lactation.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Asthmatic patients switched to Trimbow (BDP/FF/G 172/5/9 μg)	BDP/FF/G (Beclomethasone diprprionate, formoterol fumarate, glycopyrronium bromide) 172/5/9 μg	Asthmatic patients switched to BDP/FF/G 172/5/9 μg before study enrollment or at the day of enrollment due to uncontrolled asthma (a) patients who experienced one or more asthma exacerbation in the previous year and uncontrolled despite the use of b1) LABA and high dose ICS or b2) LABA and high-dose ICS + LAMA multi-inhaler triple therapy.

Primary Outcome Measures

Name	Time	Method
Asthma Control Test	6 months	Change (improvement) of Asthma Control Test score, during the 6 months of treatment (Visit 3), compared to the score at baseline. A maximum score of 25 points indicates complete asthma control, while a score less than 16 indicates very poorly controlled asthma.
Asthma Control Test - 2	6 months	The percentage of patients achieving an improvement in Asthma Control Test score of 3 points (MCID, minimum clinically important difference) or more, after the 6-month treatment (Visit 3) compared to baseline. A maximum score of 25 points indicates complete asthma control, while a score less than 16 indicates very poorly controlled asthma.

Secondary Outcome Measures

Name	Time	Method
Asthma Control Test change	6 months	The percentage of patients achieving an improvement according to asthma control levels (uncontrolled= ACT ≤15; partially controlled= 15\<ACT\<20; controlled 20≤ACT).
HRQoL	6 months	Change in Health-related QoL was assessed by measuring the 5-level EuroQoL 5-dimension component (EQ-5D-5L) index score at Visit 3 (6 months), compared to the baseline visit 1 (Week 0), regarding the assessment of the impact of Asthma on the patient's quality of life. (levels 1 to 5; 1 = indication no problem; 5 = indicating unable to/extreme problems).
Test of Adherence to Inhalers (TAI-12)	6 months	Change in Test of Adherence to Inhalers (TAI-12) score at Visit 3 (6 months) compared to baseline visit (Visit 1, week 0) regarding adherence to treatment with use of the Trimbow 172/5/9 μg pMDI (50 points = good adherence; 46 to 49 points = intermediate adherence; \< 45 points = poor adherence).
Lung function	6 months	Change in spirometry parameters: FEV1, FVC, FEV1/FVC, at Visit 3 (6 months), compared to the baseline Visit 1 (Week 0), with use of the Trimbow 172/5/9 μg pMDI.

Trial Locations

Locations (14)

AIPSMCPP Dr. Elina Smilkova; 🇧🇬 Blagoevgrad, Bulgaria

Medical Center Viva Phenix; 🇧🇬 Dobrich, Bulgaria

Medical Center Hipocrat; 🇧🇬 Gabrovo, Bulgaria

ASIMPIDPP Dr. Veselin Kalfov; 🇧🇬 Haskovo, Bulgaria

Medical Center Denitza; 🇧🇬 Montana, Bulgaria

IPASMC Dr. Kostadinka Sotirova; 🇧🇬 Pazardzhik, Bulgaria

Group practice for specialized medical care - Asthma Center Pleven; 🇧🇬 Pleven, Bulgaria

AIPSACA Dr. Talyat Cholak; 🇧🇬 Razgrad, Bulgaria

AIPSMC Dr. Svetlan Mihaylov; 🇧🇬 Stara Zagora, Bulgaria

Medical Center Third Policlinic; 🇧🇬 Stara Zagora, Bulgaria

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