Measuring Small-Airways Disease Improvement After Step-up to Extrafine TRIple or High-dose ICS/LABA in Patients Uncontrolled on Medium Dose ICS/LABA eXploring T2 Inflammation

N/ANot Yet RecruitingNCT07372521

University Hospital, Ioannina130 enrolled

Overview

The goal of this observational study is to investigate the change in small airway function through the R5-R19 index in oscillometry at 12 weeks in adults with asthma. The main question it aims to answer is: How can small airways dysfunction as evaluated by the oscillometry measure R5-19 be improved at 12 weeks, using 2 treatment arms (high-dose ICS regimen or medium dose efSITT)? Researchers will compare the efficacy of either (1) high-dose ICS combinations (high-dose extrafine BDP/FF or high-dose efSITT BDP/FF/G) or (2) medium-dose efSITT (BDP/FF/G) to determine whether there is an improvement in small airways dysfunction and better asthma control in patients who are uncontrolled on medium-dose ICS/LABA. Participants will take as drugs the Trimbow (BDP/FF/G) medium (100/6/10 μg) or high (200/6/10 μg) strengths or Foster (BDP/FF) high strength (200/6 μg); Visit the clinic three times with an one optional follow up visit, at the start (Visit 1: baseline), at 4 weeks (Visit 2), at 12 weeks (Visit 3) and the optional visit at 52 weeks (Visit 4).

All data related to the study will be recorded for each participating patient by the investigator in a separate, specially designed Case Report Form (CRF) at the start of the study. The CRF pages are specifically designed to capture the information required by the study protocol, and the investigator will enter these data into the corresponding fields, ensuring consistency with the information documented in the patient's medical record. All patients who sign the informed consent to participate in the study will be assigned a unique 5-digit identification number in the format of XX-XXX (first two digits represent the centre number and the last 3 digits the patient number), which will be recorded on all relevant study documents (CRF etc.). The patient's initials and full date of birth will not be recorded in the CRF to protect personal data, except in cases specifically permitted under the General Data Protection Regulation (GDPR). • At all 3 Visits, the following assessments will be performed to all patients: (1) Evaluation of asthma control (ACT, ACQ-5), (2) Blood Eosinophil Counts (BEC, cells/mL and %), (3) FeNO (FeNO+, MGC Diagnostics, at 50 mL/sec and at 100 and 150 mL/sec to measure alveolar NO as a marker of SAD), (4) Forced Oscillometry Technique (FOT, Resmon PRO Full V3), measuring peripheral resistance (difference between resistance at 5Hz and 19Hz, R5-19), frequency resonance (Fres), area of reactance (AX), and reactance (X5), (5) Simple spirometry, including forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC (FEF25-75%), (6) Static lung volumes by body plethysmography, including total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC), (7) At the optional Visit 4 at 52 weeks, we will collect the previous parameters and the number of exacerbations (OCS courses, emergency department visits, hospitalizations). eCRFs will be periodically reviewed by the principal investigator to minimize missing values. When NaN entries cannot be avoided, the amount, pattern, and assumed mechanism of missingness (missing completely at random, missing at random, or missing not at random) will be evaluated to determine the most appropriate statistical approach. Imputation methods may include mean or median imputation, random sample imputation, or multiple imputation, as appropriate.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Males and females out-patients aged ≥18 years providing written informed consent. \[Note: Females are eligible if they are of non-childbearing potential or, if they are of childbearing potential, using or are willing to use appropriate contraceptive measures.\] * Physician-diagnosed asthma for at least 6 months * Patients with uncontrolled asthma (ACT\<20 or ACQ-5\>1.5) on stable treatment with medium dose ICS/LABA for at least 12 weeks and with good adherence to treatment. * Evidence of SAD as expressed by FEF25-75% \<60% in spirometry. * Ability to be trained to use properly a pMDI inhaler (with or without spacer as per physician's judgement). * Documented decision in the patient's medical file for the (high-dose ICS regimen or medium dose efSITT) before the patient gets informed about his/her potential participation in the study. Exclusion Criteria: * Age \<18 years * Patients who have experienced a severe asthma exacerbation (i.e. receiving OCS for at least 3 days and/or antibiotics or need for hospitalisation) in the 4 weeks prior to the screening visit. * Refusal or inability to give informed consent. * Patients with COPD or other respiratory disease, e.g. bronchiectasis, cystic fibrosis, interstitial lung diseases or any other clinically or functionally significant lung disorder, cancer (except localized carcinomas), or other clinically significant comorbidities that may affect the outcomes measured. * Long-term oxygen therapy at home. * Pregnancy or lactation or planned pregnancy. * Patients with a history of hypersensitivity or contraindications to any of the components of the study drug. * Participation in interventional study within 30 days prior to enrolment or at least two half-life times of an investigational drug. * Patient inability or incompliance to follow physician's instructions concerning treatment or study visits or unreliability, according to the physician evaluation.

Outcomes

Primary Outcomes

Small airways function and Oscillometry

Improvement in small airways function as evaluated by the oscillometry measure R5-19 (in cmH2O/L/s) at 12 weeks compared to baseline in the whole study population

Time frame: From January 2026 to June 2027

Secondary Outcomes

Pulmonary test function results and Questionnaires

Change in R5-19 (cmH2O/L/s, at 4 weeks), Change in FEF25-75% (% pred., at 4 and 12 weeks), Change in FEV1 (L, at 4 and 12 weeks), Change in residual volume (RV) (% pred., at 4 and 12 weeks), Change in total lung capacity (TLC) (% pred., at 4 and 12 weeks), Change in FeNO (ppb, at 4 and 12 weeks), Change in asthma control test (ACT) (at 4 and 12 weeks), Change in asthma quality of life (mini-AQLQ) (at 4 and 12 weeks)