Chronic Airway Disease, Mucus Rheology and Exacerbations

NCT04339270 | Recruiting Phase 4 DMC

• 1 other identifier: RECHMPL19_0074
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 3

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• The main outcome measure is the number of exacerbations over the 12 months of follow-up.

  An exacerbation is defined according to French recommendations as an "acute event characterized by worsening of respiratory symptoms (notably cough, sputum and dyspnea) beyond \[normal\] daily variation and leading to a modification of treatment: either a simple increase in bronchodilators (in this case, a duration greater than 24 hours is required to define an exacerbation) or the addition of another treatment (antibiotic therapy and / or oral corticosteroid therapy)."

  12 months

Secondary Outcomes (116)

• The number of mild exacerbations throughout follow-up

  12 months

• The number of moderate exacerbations throughout follow-up

  12 months

• The number of severe exacerbations throughout follow-up

  12 months

• COPD Assessment Test (CAT)

  Baseline (Day 0)

• COPD Assessment Test (CAT)

  3 months

Study Arms (2)

Azithromycin according to symptoms

ACTIVE COMPARATOR

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

Drug: Azithropycin according to symptoms

Azithromycin according to rheology

EXPERIMENTAL

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

Drug: Azithromycin according to rheology or symptoms

Interventions

Azithropycin according to symptoms 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 symptoms

Azithromycin according to rheology or symptoms 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.

Azithromycin according to rheology

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnancy or breastfeeding
• Patients who are prisoners or under other forms of judicial protection
• Patients under any form of guardianship
• 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.

Sponsors & Collaborators

• University Hospital, Montpellier: lead
• Rheonova: collaborator

Study Sites (3)

University Hospitals of Bordeaux

Bordeaux, France

RECRUITING

University Hospitals of Montpellier

Montpellier, 34925, France

RECRUITING

University Hospitals of Toulouse

Toulouse, France

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

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

Study Officials

• Jérémy Charriot, MD

  University Hospital, Montpellier

  STUDY DIRECTOR

Central Study Contacts

Jérémy Charriot, MD

CONTACT

04 67 33 67 33; j-charriot@chu-montpellier.fr

Arnaud BOURDIN, MD

CONTACT

04 67 33 67 33; a-bourdin@chu-montpellier.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: CASA-Q scoring is performed by the patient and then sealed away from investigator-view. Similarly, mucus rheology results are blinded. The patient does not know what arm he/she is in, as so does not know exactly why the prescription was made or not. Similarly, investigators/outcome assessors are blinded to both CASA-Q scores and sputum rheology. The prescription strategy is determined according to an algorithm, and investigators/outcome assessors do not know what arm the patient is in nor exactly why a prescription was made or not.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial comparing outcomes in 2 parallel arms (36 vs 36 patients).

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 9, 2020
• Study Start: February 3, 2023
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: As close to "real time" as possible, the following supporting information will be made public: * Study Protocol (to be published in an appropriate journal). * Statistical Analysis Plan * Participant Information materials * Analytic code These will be posted and registered on osf.io and/or clinicaltrials.gov (if not published). Datasets can be requested after the publication process has been completed.
• Access Criteria: The conditions under which members of the public will be granted access to datasets are: * The data will be used/examined in a not-for-profit manner; * The data will not be used in an attempt to identify a participant or group of participants; * The user does not work for a private insurance company; * The data will not be used in support of any kind of private insurance policy or health penalties; * The data will be used/examined for the advancement of science/teaching while respecting participant/patient privacy and rights; * The user will state why they wish to access the data. * The appropriate CNIL approval has been obtained by the user.

Locations

FR (3)