Molecular Signatures Associated With Response to ICS Treatment in Patients With COPD Stratified by Eosinophil Levels (3TR-ICS-COPD)

The 3TR-ICS COPD study is an international, multicentre, randomized, parallel, controlled study that will recruit clinically stable former smokers COPD patients (with no exacerbations in the previous 8 weeks) on treatment with dual long-acting bronchodilators (LABA+LAMA), minimum 8 weeks of usage, not receiving ICS (either naïve or > 3 months since last usage). The overall objective of this clinical trial is to identify the molecular signatures associated with the molecular response to ICS treatment in patients with COPD stratified by the levels of circulating eosinophils, and the potential influence of the pulmonary microbiome

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Budesonide

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rosa Faner; Phone Number: +34932775400; Email: rfaner@recerca.clinic.cat
• Study Contact Backup: Name: Maria Joyera; Email: joyera@recerca.clinic.cat

Study Locations

• Germany
  • Marburg, Germany
    • Recruiting
    • Philips University of Marburg
    • Contact: Peter Alter
• Netherlands
  • Groningen, Netherlands
    • Recruiting
    • Academisch Ziekenhuis Groningen
    • Contact: Marteen van den Berge
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Clínic Barcelona
    • Contact: Alvar Agustí
  • Palma de Mallorca, Spain, 07120
    • Recruiting
    • Son Espases
    • Contact: Francisco de Borja Cosio
• United Kingdom
  • Leicester, United Kingdom
    • Not yet recruiting
    • University of Leicester
    • Contact: Christopher Brightling
  • London, United Kingdom
    • Not yet recruiting
    • Imperial College London
    • Contact: Lydia J Finney

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patients ≥40 years of age.
• ≥ 10 pack-years smoking.
• Former smokers (≥6 months).
• post-bronchodilator FEV1/FVC<0.70.
• FEV1 ≥30 <80% ref.
• Signed written informed consent form.
• On regular treatment with dual long-acting bronchodilators (LABA+LAMA), minimum 8 weeks of usage.
• Women of child-bearing potential* must have a negative pregnancy test in serum or urine before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.
• Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function.

Exclusion Criteria:

• Presence of other respiratory disorders, (i.e. current physician diagnosis of asthma, early life history of asthma (<21 years) a previous clinical diagnosis of bronchiectasis, interstitial lung disease, pulmonary eosinophilia).
• Long-term oxygen therapy or non-invasive mechanical ventilation at home.
• Current smokers.
• Active cancer.
• Use of ICS in the 3 months prior to the recruitment.
• Participating in another randomized trial.
• Not likely to complete the study.
• Pregnant or breastfeeding females.
• Exacerbations in the previous 8 weeks.
• Primary or secondary immunodeficiency.
• Immunosuppression or regular oral corticosteroid treatment.
• Allergy to IMP's excipients.
• Any circumstances which could contradict study participation and lead the investigator to assess the patient as unsuitable for study participation for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ICS treatment	Drug: Budesonide; receive, on top of their usual treatment Budesonide dry powder inhaler, 400 mcg/12 hours for 8 weeks
No Intervention: No ICS treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Significant molecular changes in COPD stratified by their blood eosinophil counts.	Significant molecular changes (p<0.05, and/or FDR<0.05) (e.g. microbiome and/or transcriptome and/or proteins and/or epigenetics) in sputum, nasal and oropharyngeal swabs, urine and/or blood associated with ICS treatment vs. no ICS treatment (usual care), in COPD stratified by their blood eosinophil counts.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Significant molecular changes in COPD with different airflow limitation severities.	Significant molecular changes (p<0.05, and/or FDR<0.05) (e.g. microbiome and/or transcriptome and/or proteins and/or epigenetics) in sputum, nasal and oropharyngeal swabs, urine and/or blood associated with ICS treatment vs. no ICS treatment (usual care), in COPD with different airflow limitation severities.	8 weeks

Collaborators and Investigators

• Sponsor: Maria Joyera Rodríguez

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; Budesonide
• Other Study ID Numbers: 2023-505245-13-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No