Immuno-inflammatory Response of Erdosteine in COPD

NCT07329946 | Not Yet Recruiting

• 1 other identifier: 400.141CRC
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic obstructive pulmonary disease (COPD) remains a major contributor to global morbidity and mortality, exposing healthcare systems to a significant economical and social load. Indeed, acute severe COPD exacerbations are the events that contribute most to the overall disease burden. Current management strategies are aimed at maximizing symptom-free periods, reduce hospitalizations, improve exercise tolerance, overall health status, and quality of life. Key pathophysiological mechanisms involved in COPD exacerbations (defined as acute worsening of respiratory symptoms) include oxidative stress, acute on chronic inflammation, and mucus hypersecretion. Agents with antioxidant, anti-inflammatory, and mucolytic properties can help reduce exacerbation frequency. Erdosteine is a new-generation mucoactive molecule developed to overcome the limitations associated with traditional mucolytics. In fact, in addition to its mucolytic effects, erdosteine exhibits antioxidant and anti-inflammatory activities and may reduce bacterial adhesion to airway surfaces - features that may be beneficial in the prevention and management of exacerbations. Preliminary clinical findings (EQUALIFE and RESTORE studies) suggest that erdosteine, in add-on to chronic inhaled therapy, can reduce exacerbation rates, shorten hospital stay, and improve health-related quality of life in patients with COPD. However, studies that have investigated the pathobiological mechanisms behind such clinical effects are lacking. The present study was constructed in order to investigate the mechanism of action of erdosteine on inflammation, oxidative stress pathways and immune response in patients with COPD. The secondary objectives of the study are to evaluate the effect of erdosteine on lung function tests in patients with COPD; to explore the effect of erdosteine on respiratory and COPD-related symptoms in patients with COPD; to assess the effect of erdosteine on exercise tolerance in patients with COPD. In order to do so, the investigator designed a pragmatic, low intervention, two-arms, monocenter, open-label, prospective, randomized, controlled trial, set in clinical practice. A total of 30 patients will be randomized by means of a 1:1 random allocation. The active group (15 patients) will be assigned to Treatment Arm A (Erdosteine \[Esteclin®\] 300 mg, 1 tablet twice daily for 30 days), while the control group (15 patients) will be assigned to Treatment Arm B (Standard of Care - current standard inhalation therapy in use).

Conditions

COPD

Keywords

COPD; ERDOSTEINE

Outcome Measures

Primary Outcomes (2)

• Changes in transcriptomics of pro-inflammatory and anti-inflammatory cytokines in COPD patients exposed to erdosteine.

  Peripheral blood will be analyzed for immunological profiling in patients treated with standard of care only and patients also exposed to Erdosteine at baseline and after 4 weeks of treatment. Cytokine/chemokine profiles will be quantified in cell culture supernatants using the Bio-Plex Pro Human Cytokine 27-plex Assay. RNA extraction from whole blood will be performed to identify expression levels of molecules involved in immune response: CARD6, CASP1, CASP4, CCL2, HLA-A, IFITM1, IFNA1, IFNAR1, IL1β, IL6, IL8, IL10, IL17, IL18, IL22, ISG20, TGF-β, NLRP3, NLRP4, VCAM1. Betaactin (ACTB) and glyceraldeyde-3-phosphate dehydrogenase (GAPDH) will be used as housekeeping genes. The results for the gene expression analyses will be presented as the average of the relative expression units (%) to an internal reference sample and normalized to the housekeeping genes GAPDH and ACTB.

  4 weeks

• Changes in transcriptomics of oxidative stress signaling pathways in COPD patients exposed to erdosteine.

  Peripheral blood will be analyzed for oxidative stress profiling in patients treated with standard of care only and patients also exposed to Erdosteine at baseline and after 4 weeks of treatment. Oxidative stress will be quantified in cell culture supernatants using the Bio-Plex Pro Human Cytokine 27-plex Assay. RNA extraction from whole blood will be performed to identify expression levels of molecules involved in oxidative stress: APOE, CAT, DUSP1, GPX2, GPX3, MPO, NOS2, NOX4, NUDT1, SOD2. Betaactin (ACTB) and glyceraldeyde-3-phosphate dehydrogenase (GAPDH) will be used as housekeeping genes. The results for the gene expression analyses will be presented as the average of the relative expression units (%) to an internal reference sample and normalized to the housekeeping genes GAPDH and ACTB.

  4 weeks

Secondary Outcomes (3)

• To assess the effect of erdosteine on mMRC dyspnea scale in patients with COPD

  4 weeks

• To assess the effect of erdosteine on distance covered during the six minute walk test in patients with COPD

  4 weeks

• To assess the effect of erdosteine on CAT (COPD assessment test) in patients with COPD

  4 weeks

Other Outcomes (4)

• To evaluate the effect of erdosteine on dynamic lung volumes in patients with COPD

  4 weeks

• To assess the effect of erdosteine on static volumes in patients with COPD

  4 weeks

• To evaluate the effect of erdosteine on lung diffusion capacity in patients with COPD

  4 weeks

Study Arms (2)

ARM A - Erdosteine treatment

EXPERIMENTAL

Patients will be randomized to receive Erdosteine \[Esteclin®\] 300 mg, 1 tablet twice daily for 30 days

Drug: Erdosteine; Drug: Standard of Care (SOC)

ARM B - Standard of care

PLACEBO COMPARATOR

Patients will be randomized to receive current standard inhalation therapy in use

Drug: Standard of Care (SOC)

Interventions

Erdosteine DRUG

Erdosteine tablets 300 mg, 1 tablet orally every 12 hours (twice daily) for 30 days

Also known as: Esteclin

ARM A - Erdosteine treatment

Standard of Care (SOC) DRUG

Long acting beta-2 agonists and Long acting muscarinic antagonists in association (LABA/LAMA) with or without inhaled corticosteroids (LABA/LAMA/ICS) depending on the chronic inhaled home treatment. Dosage and posology will change depending on the molecules and the devices (once daily in case of umeclidinium bromide/vilanterol 55/22 mcg or fluticasone/umeclidinium bromide/vilanterol 92/55/22 or twice daily in case of budesonide/formoterol/glycopyrronium 160/7.2/4.8 mcg and beclometasone/formoterol/glycopyrronium 87/5/9 mcg)

ARM A - Erdosteine treatment; ARM B - Standard of care

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 45 years
• A confirmed COPD diagnosis at least 12 months prior to enrollment
• Stable clinical conditions, defined as no exacerbations or respiratory infections of any severity in the last 3 months before enrollment
• Moderate to Severe airflow obstruction (FEV1 30-80 %predicted post bronchodilation.
• No hospitalizations for any cause in the 3 months prior to enrollment
• Ability to perform repeatable pulmonary function tests
• Chronic inhaled therapy with LAMA/LABA or LAMA/LABA/ICS with no changes in dosage in the last 3 before enrollment

You may not qualify if:

• NYHA class III and IV heart failure
• Unstable arrythmia
• Active malignancy (solid or blood)
• Chronic treatment with systemic corticosteroids or immunosuppressants
• Immune depression
• Known hypersensitivity to erdosteine
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Pierachille Santus, MD, PhD: lead

Study Sites (1)

L. Sacco Hospital

Milan, 20157, Italy

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

erdosteine; Standard of Care

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Pierachille Santus Professor, MD, PhD

CONTACT

0039 0239042801; pierachille.santus@unimi.it

Dejan Radovanovic, MD, PhD

CONTACT

0039 0239042372; dejan.radovanovic@unimi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: January 9, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

IT (1)