Clinical trial NCT06678191: Investigation of Fixed Triple Inhaled Combination in Asthmatic Patients, in a Real-life Setting
Official title: Effectiveness of BDP/FF/G 172/5/9 Fixed Triple Combination on Symptom Scores in Asthma Patients After 6 Months Treatment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Asthma, Chronic Obstructive Pulmonary Disease (COPD)
Asthma Bronchiale
Keywords: Asthma therapy
Fixed triple inhalation treatment
Trimbow
Lead sponsor: Chiesi Hungary Ltd.
Sponsor class: INDUSTRY
First posted: 2024-11-07
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Asthma patients treated at GINA step 5, uncontrolled with ICS-LABA, containing high dose ICS.

Brief summary: The mainstay of asthma treatment are ICSs, mostly 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 authorisation 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. Also, there is scarcity of data regarding the phenotypes of asthmatics who benefit the most from the use of fixed triple combinations.

Detailed description: Study design Multicentre, 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 containing treatment in asthmatics.

Dosage regimen and administration Name of the product: Trimbow 172 micrograms/5 micrograms/9 micrograms pressurised inhalation, solution (henceforth abbreviated as Trimbow 172/5/9 μg pMDI). 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).
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 and attending pulmonology 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 800.
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, and patients should only be considered for inclusion in the study after a prior therapeutic decision has been made by a pulmonologist. Patient enrolment can take place after the patient has been fully informed about the purpose of the study and all of its details, and the patient has read and signed the patient information leaflet and patient 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, previous and current asthma therapies, asthma specific assessment (including ACT), exacerbation history, post-dose lung function values (if spirometry data is available), laboratory results (if a laboratory test is performed during the visit or was performed recently), results of other medical examinations (e.g., chest X-ray) if performed regardless of the study, maintenance and reliever inhaled \& non-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. Patients will then attend two additional visits 30 days and 6 months after enrolment as per routine clinical practice (Visits 2 and 3). During these visits, data will also be recorded, once again, according to routine clinical practice. Assessing the usage of rescue medications and patient adherence are also planned with the use of electronic health record system (EESZT)-verified prescription dispensations (optional for investigators). Visit 4 will be a long-term follow-up to assess the exploratory endpoint of exacerbations rates.

   If the patient's maintenance therapy changes during the study as decided by the treating pulmonologist, and the patient is no longer receiving Trimbow 172/5/9 μg pMDI, the patient will be automatically excluded from this NIS. The fact of the therapy modification and its exact date must be recorded on the "current medication" form 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 on the eCRF platform in accordance with section 9 of this protocol ('Collection, recording and reporting of medication safety data').

   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. The data to be recorded will be detailed in the study data sheet that forms part of the protocol. The data is recorded in the eCRF (MrAgent - Medisol Development Ltd., see also at 10.1.) system, with consideration to the current professional and legal regulations.
4. Start and duration of the study The first patient enrolment will take place after receiving approval from the National Public Health Center (NPHC), based on a beneficial assessment of the Medical Research Council of Hungary. The study is planned to start on September 16, 2024. Accordingly, first patient first visit (FPFV) is also planned to take place in September, 2024. The launch of the participating centres is planned in two waves, in the autumn of 2024 and in the spring of 2025. Each centre will have 12 months to enrol patients. After the last visit of the last patient (LPLV), centres will have one month to collect all missing data / correct any data flagged as queries during monitoring. Thus, the LPLV will take place on Oct 31, 2026 (primary endpoint) and 30 April, 2027 (exploratory endpoint), respectively. The study is planned to be concluded on August 31, 2027.
5. Data to be recorded during the visits A total of 4 visits will be performed for the assessment of the primary and secondary endpoints during the study. The table below summarises the data collection to be carried out during the visits separately. The patient may be enrolled in the study and their data may only be recorded, if these data would also have been 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 (± 2-3 workdays)
   * Visit 3: 6 months after enrolment (± 5-7 workdays)
   * Visit 4: 12 months after enrolment (± 10-15 days)

Eligibility criteria: INCLUSION CRITERIA:

* Physician-confirmed clinical diagnosis of asthma according to GINA guidelines and treated for at least 3 years before inclusion
* Patients ≥ 18 years of age in ambulatory care
* Uncontrolled asthma according to the physician's clinical assessment despite the use of

  1. LABA - high dose ICS OR
  2. LABA - high-dose ICS + LAMA multi-inhaler triple therapy for a minimum of three months.
* Patients who are eligible for the use of Trimbow 172/5/9 μg pMDI according to the SmPC and the financing protocol for asthma

  1. At least on exacerbation, requiring systemic (oral or intravenous) corticosteroids in the previous 12 months
  2. Uncontrolled asthma (ACT≤15)
  3. FEV1\<80% at baseline
* Inhaled asthma therapy was changed to Trimbow 172/5/9 μg pMDI no more than 1 week prior to OR on the day of study inclusion
* Patient provided written, informed consent to study participation

EXCLUSION CRITERIA:

* Participation in any clinical trial within 30 days prior to enrolment
* Patients hospitalized due to an exacerbation of their asthma within the last 4 weeks prior to enrolment
* Another respiratory condition, apart from asthma or COPD, that may interfere with the effectiveness of the treatment studied AND/OR another important clinical situation that may interfere with patient's compliance with the treatment.
* Continuous use of oral (\>5 mg prednisolone/day OR \>4 mg methylprednisolone/day) OR intravenous corticosteroids CHMED_2024/01 Prof. Dr. Lilla Tamási 8(17)
* Use of continuous oxygen therapy
* Any malignant disease in the last 5 years
* Tuberculosis (active or anamnestic)
* Actual or previous use of biologics for asthma treatment in the past 12 months
* All exclusion criteria listed in Trimbow 172/5/9 μg pMDI SmPC

Primary outcomes:
measure: Asthma control Test
timeFrame: 6 months
measure: Asthma control Test 2
timeFrame: 6 months
Secondary outcomes:
measure: Asthma control test change
timeFrame: 6 months
measure: HRQoL
timeFrame: 6 months
measure: Adherence
timeFrame: 6 months
measure: Lung function
timeFrame: 6 months
Other outcomes:
measure: Exacerbations
timeFrame: 12 months
Locations:
city: Budapest
country: Hungary
facility: Kispesti Egészségügyi Intézet Tüdőgondozó, Ernyőképszűrő állomás
city: Budapest
country: Hungary
facility: Országos Korányi Pulmonológiai Intézet (OKPI)
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, Általános Orvostudományi Kar, Pulmonológiai Klinika
city: Budapest
country: Hungary
facility: Szent Kristóf Szakrendelő XI. Kerületi Tüdőgondozó
city: Budapest
country: Hungary
facility: Szent Kristóf Szakrendelő XXII. Kerületi Tüdőgondozó
city: Budapest
country: Hungary
facility: XVI. Kerület Kertvárosi Egészségügyi Szolgálata, Tüdőgyógyászat
city: Békéscsaba
country: Hungary
facility: Békés Megyei Központi Kórház, 2. Tüdőgyógyászat szakrendelés - 1. rendelés
city: Csorna
country: Hungary
facility: Csornai Margit Kórház Tüdőbeteggondozó Intézet
city: Debrecen
country: Hungary
facility: DE Klinikai Központ, Tüdőgyógyászati Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Kenézy Gyula Egyetemi Kórház Pulmonológiai Részleg
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ Allergológiai Szakrendelés
city: Deszk
country: Hungary
facility: SZTE SZAKK Deszki Multidiszciplináris Centrum
city: Dunakeszi
country: Hungary
facility: Dunakeszi-SZTK Nonprofit Kft. Tüdőgyógyászat
city: Esztergom
country: Hungary
facility: Vaszary Kolos Kórház Tüdőgondozó Esztergom
city: Fehérgyarmat
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház 1. Tüdőgyógyászat Szakrendelés
city: Gyöngyös
country: Hungary
facility: Bugát Pál Kórház Tüdőbeteg Gondozó Intézet
city: Győr
country: Hungary
facility: Petz Aladár Megyei Oktató Kórház
city: Hajdúböszörmény
country: Hungary
facility: Hajduböszörmény ESZ-V Nonprofit Kft Tüdőgyógyászat
city: Jászberény
country: Hungary
facility: Tüdőgondozó / Szent Erzsébet Kórház
city: Kalocsa
country: Hungary
facility: Szent Kereszt Kórház Kalocsa,Tüdőgyógyászati Szakrendelés
city: Kaposvár
country: Hungary
facility: Somogy Megyei Kaposi Mór Oktató Kórház
city: Keszthely
country: Hungary
facility: Keszthelyi Kórház Tüdőgondozó
city: Kistelek
country: Hungary
facility: Kisteleki Egészségügyi Központi Nonprofit Kft.
city: Kisvárda
country: Hungary
facility: Szent Damján Görögkatolikus Kórház Tüdőgyógyászati gondozó 1.
city: Komárom
country: Hungary
facility: Selye János Kórház Tüdőgyógyászati Szakellátás
city: Kunszentmárton
country: Hungary
facility: Kunszentmárton Városi Egészségügyi Központ Tüdőgyógyászat
city: Marcali
country: Hungary
facility: Szaplonczay Manó Marcali Kórház Tüdőgyógyászati Szakrendelés
city: Mosonmagyaróvár
country: Hungary
facility: Karolina Kórház-Rendelőintézet Mosonmagyaróvár
city: Mátraháza
country: Hungary
facility: Mátrai Gyógyintézet Légzőszervi szakrendelés
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Kórház
city: Nyírbátor
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár- Bereg Megyei Kórházak és Egyetemi Oktatókórház Megyei-Városi Tüdőgondozó
city: Orosháza
country: Hungary
facility: Orosházi Kórház Tüdőgondozó
city: Pásztó
country: Hungary
facility: Margit Kórház Pásztó Tüdőgyógyászati Szakrendelés
city: Pécs
country: Hungary
facility: Egyesített Egészségügyi Intézmények Tüdőgondozó
city: Sarkad
country: Hungary
facility: Sarkadi Kistérségi Járóbeteg Szakellátó Központ
city: Siófok
country: Hungary
facility: Siófoki Kórház-Rendelőintézet Tüdőgondozó
city: Szeged
country: Hungary
facility: Csongrád Megyei Mellkasi Betegségek Szakkórháza, Tüdőgondozó Intézet
city: Szolnok
country: Hungary
facility: Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintézet Tüdőgyógyászati Szakrendelés
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatókórház
city: Székesfehérvár
country: Hungary
facility: Alba Szűrőközpont
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Egyetemi Oktató Kórház, Tüdőbeteg Gondozó, Városkörnyék I. Szakrendelés Székesfehérvár
city: Törökbálint
country: Hungary
facility: Református Pulmonológiai Centrum, Törökbálint
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Kórház
Study officials:
References: