Chronic Airway Disease, Mucus Rheology and Exacerbations

NCT ID: NCT04339270

Last Updated: 2024-07-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-03
• Study Completion Date: 2026-02-28

Brief Summary

The main objective of this trial is to compare the exacerbation number over 12 months of follow-up between a group of patients with COPD treated according to standardized management (azithromycin prescribed in the event of severe sputum according to the CASA-Q score , standardized comparator arm) and a similar group in which azithromycin is prescribed based on mucus rheology (experimental arm) or CASA-Q.

Detailed Description

The secondary objectives are to compare between the 2 arms:

• exacerbation number according to their severity (observed throughout the duration of the study);
• the evolution of the symptoms, the rheology of the sputum, and the pulmonary function (measurements repeated every three months);
• medication consumption and adverse events (monitored throughout the duration of the study);
• patient trajectories during follow-up;
• the overall clinical improvement at the end of the study and the evolution of the quality of life (measurements repeated every 3 months);
• the change in biomarkers of interest (baseline versus end of study).

Conditions

Chronic Obstructive Pulmonary Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Azithromycin according to symptoms

Patients randomized to this arm will be prescribed azithromycin in function of their symptoms.

Group Type: ACTIVE_COMPARATOR

Azithropycin according to symptoms

Intervention Type: DRUG

Patients randomized to the "standardized comparator arm" will benefit from the standard treatment for COPD, including with regard to the prescription of azithromycin in case of severe sputum complaints (here defined by a CASA-Q sputum symptoms score <70 to homogenize practices between centers).

CASA-Q will be evaluated every 3 months.

• If the patient has a sputum symptoms score <70, a prescription for 3 months of azithromycin treatment will be initiated. This prescription can be renewed every 3 months during the 12 months of follow-up planned in this study, if the patient continues to obtain a sputum symptoms score <70.
• If the patient has a sputum symptoms score> 70, management is not changed.

Azithromycin according to rheology

Patients randomized to this arm will be prescribed azithromycin in function of their sputum rheology.

Group Type: EXPERIMENTAL

Azithromycin according to rheology or symptoms

Intervention Type: DRUG

Treatment according to standard COPD management, except for the prescription of azithromycin, which will be prescribed in function of mucus rheology or as a function of sputum complaints (here defined by a CASA-Q sputum symptoms score <70).

The rheology of mucus will be quantified every 3 months.

• If the patient has spontaneous or induced sputum, and this sputum has a critical constraint (tau-C) > 39, a prescription for 3 months of azithromycin treatment will be initiated. This prescription may be renewed every 3 months during the 12 months of follow-up planned in this study.
• If the patient has a sputum symptoms score <70, a prescription for 3 months of azithromycin treatment will be initiated. This prescription can be renewed every 3 months during the 12 months of follow-up planned in this study, if the patient continues to obtain a sputum symptoms score <70.
• If the patient has a sputum symptoms score> 70, management is not changed.

Interventions

Azithropycin according to symptoms

Patients randomized to the "standardized comparator arm" will benefit from the standard treatment for COPD, including with regard to the prescription of azithromycin in case of severe sputum complaints (here defined by a CASA-Q sputum symptoms score <70 to homogenize practices between centers).

CASA-Q will be evaluated every 3 months.

• If the patient has a sputum symptoms score <70, a prescription for 3 months of azithromycin treatment will be initiated. This prescription can be renewed every 3 months during the 12 months of follow-up planned in this study, if the patient continues to obtain a sputum symptoms score <70.
• If the patient has a sputum symptoms score> 70, management is not changed.

Intervention Type: DRUG

Azithromycin according to rheology or symptoms

Treatment according to standard COPD management, except for the prescription of azithromycin, which will be prescribed in function of mucus rheology or as a function of sputum complaints (here defined by a CASA-Q sputum symptoms score <70).

The rheology of mucus will be quantified every 3 months.

• If the patient has spontaneous or induced sputum, and this sputum has a critical constraint (tau-C) > 39, a prescription for 3 months of azithromycin treatment will be initiated. This prescription may be renewed every 3 months during the 12 months of follow-up planned in this study.
• If the patient has a sputum symptoms score <70, a prescription for 3 months of azithromycin treatment will be initiated. This prescription can be renewed every 3 months during the 12 months of follow-up planned in this study, if the patient continues to obtain a sputum symptoms score <70.
• If the patient has a sputum symptoms score> 70, management is not changed.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjets between 40 - 85 years (included)
• Written and signed informed consent form
• Subjects must be able to attend all planned visits and comply with all test procedures
• Beneficiary of or affiliated with the French social security system
• Man or woman with chronic obstructive pulmonary disease for at least 1 year defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and validated by the clinical investigator
• Optimal treatment according to GOLD class severity C or D recommendations
• >=3 exacerbation (regardless of severity: mild-moderate-severe) or ≥ 1 severe exacerbations (requiring hospitalization) in the past 12 months
• Spontaneous or induced sputum production
• Electrocardiogram: corrected distance between Q and T waves (QTC) <450 ms in men, QTC <470 ms in women
• Normal audiogram for age or absence of contraindication to azithromycin for long course according to Oto-Rhino-Laryngological specialist opinion

Exclusion Criteria

• Pregnancy or breastfeeding
• Patients who are prisoners or under other forms of judicial protection
• Patients under any form of guardianship
• Participation in another interventional protocol, (current or during the month preceding inclusion)
• Received azithromycin in the past 3 months
• Patient whose primary diagnosis is bronchial dilation based on CT scan documentation
• Known hypersensitivity to azithromycin, erythromycin, any other macrolide, ketolide or any of the excipients of the azithromycin-based specialty used
• Concomitant use of medication contraindicated with azithromycin (dihydroergotamine, ergotamine, cisapride, colchicine)
• Other respiratory diseases or associated lung infections
• Severe hepatic insufficiency and severe cholestasis (a liver biological test will be carried out if clinical suspicion)
• Renal impairment with creatinine clearance < 40 mL/min
• Patients with hematological malignancies who have undergone allogeneic hematopoietic stem cell transplantation
• Patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary disease) due to the presence of lactose in the specialty Zithromax.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rheonova

UNKNOWN

Sponsor Role: collaborator

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jérémy Charriot, MD

Role: STUDY_DIRECTOR

University Hospital, Montpellier

Locations

University Hospitals of Bordeaux

Bordeaux, , France

Site Status: RECRUITING

University Hospitals of Montpellier

Montpellier, , France

Site Status: RECRUITING

University Hospitals of Toulouse

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Jérémy Charriot, MD

Role: CONTACT

j-charriot@chu-montpellier.fr

04 67 33 67 33

Arnaud BOURDIN, MD

Role: CONTACT

a-bourdin@chu-montpellier.fr

04 67 33 67 33

Other Identifiers

RECHMPL19_0074

Identifier Type: -

Identifier Source: org_study_id