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

NCT07372521 | Not Yet Recruiting

• 2 other identifiers: RMDUoI-001University Hospital Ioannina
• Study Type: observational
• Target: 130
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Asthma

Keywords

Asthma; Clinical Trials, Phase IV as Topic; Drug Therapy, Combination; LABA; LAMA; ICS; Oscillometry; Respiratory Function Tests; FeNO

Outcome Measures

Primary Outcomes (1)

• 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

  From January 2026 to June 2027

Secondary Outcomes (1)

• Pulmonary test function results and Questionnaires

  From January 2026 to June 2027

Other Outcomes (1)

• Optional evaluation (at 52 weeks)

  From January 2026 to June 2027

Study Arms (1)

Males and females out-patients aged ≥18 years with uncontrolled asthma on ICS/LABA treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients with physician-diagnosed asthma, recruited from outpatient and/or inpatient clinics at participating hospitals.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Ioannina: lead
• Attikon Hospital: collaborator
• 424 General Military Hospital: collaborator
• George Papanicolaou Hospital: collaborator
• University Hospital of Patras: collaborator
• University Hospital, Alexandroupolis: collaborator

Related Publications (16)

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  PMID: 10573240 BACKGROUND

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• Galant SP, Kuks PJM, Kole TM, Kraft M, Siddiqui S, Fabbri LM, Beghe B, Rabe KF, Papi A, Brightling CE, Singh D, Kocks JWH, Franzini L, Vonk JM, Kerstjens HAM, Heijink IH, Pouwels SD, Slebos DJ, van den Berge M. Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study. Lancet Respir Med. 2025 Nov;13(11):990-1000. doi: 10.1016/S2213-2600(25)00283-8. Epub 2025 Sep 29.

  PMID: 41038213 BACKGROUND

• 2025 GINA Strategy Report [Internet]. Global Initiative for Asthma - GINA 2025 [cited 2025 Oct 28]. Available from: https://ginasthma.org/2025-gina-strategy-report/).

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• Papi A, Singh D, Virchow JC, Canonica GW, Vele A, Georges G. Normalisation of airflow limitation in asthma: Post-hoc analyses of TRIMARAN and TRIGGER. Clin Transl Allergy. 2022 Apr 17;12(4):e12145. doi: 10.1002/clt2.12145. eCollection 2022 Apr.

  PMID: 35450196 BACKGROUND

• Quaranta VN, Montagnolo F, Portacci A, Dragonieri S, Granito M, Rociola G, Ferrulli S, Maselli L, Carpagnano GE. Steady Quiet Asthma Without Biologics: One-Year Outcomes of Single-Inhaler Triple Therapy for Severe Asthma with Small Airway Dysfunction. J Clin Med. 2025 Aug 7;14(15):5602. doi: 10.3390/jcm14155602.

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• Carpagnano GE, Scioscia G, Lacedonia D, Stornelli SR, Irene Quarato CM, Soccio P, Resta O, Foschino Barbaro MP. Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients. Pulm Pharmacol Ther. 2020 Feb;60:101879. doi: 10.1016/j.pupt.2019.101879. Epub 2019 Dec 20.

  PMID: 31866498 BACKGROUND

• Scichilone N, Battaglia S, Sorino C, Paglino G, Martino L, Paterno A, Santagata R, Spatafora M, Nicolini G, Bellia V. Effects of extra-fine inhaled beclomethasone/formoterol on both large and small airways in asthma. Allergy. 2010 Jul;65(7):897-902. doi: 10.1111/j.1398-9995.2009.02306.x. Epub 2010 Jan 28.

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• Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S, Zuccaro F, Vele A, Kots M, Georges G, Petruzzelli S, Canonica GW. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019 Nov 9;394(10210):1737-1749. doi: 10.1016/S0140-6736(19)32215-9. Epub 2019 Sep 30.

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• Kraft M, Richardson M, Hallmark B, Billheimer D, Van den Berge M, Fabbri LM, Van der Molen T, Nicolini G, Papi A, Rabe KF, Singh D, Brightling C, Siddiqui S; ATLANTIS study group. The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study. Lancet Respir Med. 2022 Jul;10(7):661-668. doi: 10.1016/S2213-2600(21)00536-1. Epub 2022 Mar 2.

  PMID: 35247313 BACKGROUND

• Postma DS, Brightling C, Baldi S, Van den Berge M, Fabbri LM, Gagnatelli A, Papi A, Van der Molen T, Rabe KF, Siddiqui S, Singh D, Nicolini G, Kraft M; ATLANTIS study group. Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study. Lancet Respir Med. 2019 May;7(5):402-416. doi: 10.1016/S2213-2600(19)30049-9. Epub 2019 Mar 12.

  PMID: 30876830 BACKGROUND

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Central Study Contacts

Konstantinos Kostikas, Professor

CONTACT

+302651007536; ktkostikas@uoi.gr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 52 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Head Respiratory Medicine, University of Ioannina, Greece

Study Record Dates

• First Submitted: January 11, 2026
• First Posted: January 28, 2026
• Study Start: January 19, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting after the date of publication.
• Access Criteria: Individual participant data (IPD) and supporting information from this trial will be freely available to qualified researchers following the publication of the trial results. Access will include the de-identified participant-level dataset, study protocol, and statistical analysis plan. Researchers may request the data through the corresponding data repository link.