Clinical trial NCT04339270: Chronic Airway Disease, Mucus Rheology and Exacerbations
Official title: Chronic Airway Disease, Mucus Rheology and Exacerbations: a Randomized Controlled Trial of COPD Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: Rheonova
First posted: 2020-04-09
Enrollment: 72
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial comparing outcomes in 2 parallel arms (36 vs 36 patients).
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: The main outcome measure is the number of exacerbations over the 12 months of follow-up.
timeFrame: 12 months
Secondary outcomes:
measure: The number of mild exacerbations throughout follow-up
timeFrame: 12 months
measure: The number of moderate exacerbations throughout follow-up
timeFrame: 12 months
measure: The number of severe exacerbations throughout follow-up
timeFrame: 12 months
measure: COPD Assessment Test (CAT)
timeFrame: Baseline (Day 0)
measure: COPD Assessment Test (CAT)
timeFrame: 3 months
measure: COPD Assessment Test (CAT)
timeFrame: 6 months
measure: COPD Assessment Test (CAT)
timeFrame: 9 months
measure: COPD Assessment Test (CAT)
timeFrame: 12 months
measure: Sino Nasal Outcome Test 22
timeFrame: Baseline (Day 0)
measure: Sino Nasal Outcome Test 22
timeFrame: 3 months
measure: Sino Nasal Outcome Test 22
timeFrame: 6 months
measure: Sino Nasal Outcome Test 22
timeFrame: 9 months
measure: Sino Nasal Outcome Test 22
timeFrame: 12 months
measure: Cough and sputum assessment questionnaire (CASA-Q)
timeFrame: Baseline (Day 0)
measure: Cough and sputum assessment questionnaire (CASA-Q)
timeFrame: 3 months
measure: Cough and sputum assessment questionnaire (CASA-Q)
timeFrame: 6 months
measure: Cough and sputum assessment questionnaire (CASA-Q)
timeFrame: 9 months
measure: Cough and sputum assessment questionnaire (CASA-Q)
timeFrame: 12 months
measure: Visual analogue scale for dyspnea
timeFrame: Baseline (Day 0)
measure: Visual analogue scale for dyspnea
timeFrame: 3 months
measure: Visual analogue scale for dyspnea
timeFrame: 6 months
measure: Visual analogue scale for dyspnea
timeFrame: 9 months
measure: Visual analogue scale for dyspnea
timeFrame: 12 months
measure: Visual analogue scale for coughing
timeFrame: Baseline (Day 0)
measure: Visual analogue scale for coughing
timeFrame: 3 months
measure: Visual analogue scale for coughing
timeFrame: 6 months
measure: Visual analogue scale for coughing
timeFrame: 9 months
measure: Visual analogue scale for coughing
timeFrame: 12 months
measure: Visual analogue scale for sputum production
timeFrame: Baseline (Day 0)
measure: Visual analogue scale for sputum production
timeFrame: 3 months
measure: Visual analogue scale for sputum production
timeFrame: 6 months
measure: Visual analogue scale for sputum production
timeFrame: 9 months
measure: Visual analogue scale for sputum production
timeFrame: 12 months
measure: Rheology: modulus of elasticity of mucus (G ')
timeFrame: Baseline (Day 0)
measure: Rheology: modulus of elasticity of mucus (G ')
timeFrame: 3 months
measure: Rheology: modulus of elasticity of mucus (G ')
timeFrame: 6 months
measure: Rheology: modulus of elasticity of mucus (G ')
timeFrame: 9 months
measure: Rheology: modulus of elasticity of mucus (G ')
timeFrame: 12 months
measure: Rheology: the viscous module (G '')
timeFrame: Baseline (Day 0)
measure: Rheology: the viscous module (G '')
timeFrame: 3 months
measure: Rheology: the viscous module (G '')
timeFrame: 6 months
measure: Rheology: the viscous module (G '')
timeFrame: 9 months
measure: Rheology: the viscous module (G '')
timeFrame: 12 months
measure: Rheology: The ratio G '' / G '
timeFrame: Baseline (Day 0)
measure: Rheology: The ratio G '' / G '
timeFrame: 3 months
measure: Rheology: The ratio G '' / G '
timeFrame: 6 months
measure: Rheology: The ratio G '' / G '
timeFrame: 9 months
measure: Rheology: The ratio G '' / G '
timeFrame: 12 months
measure: Rheology: the critical constraint (tau-C).
timeFrame: Baseline (Day 0)
measure: Rheology: the critical constraint (tau-C).
timeFrame: 3 months
measure: Rheology: the critical constraint (tau-C).
timeFrame: 6 months
measure: Rheology: the critical constraint (tau-C).
timeFrame: 9 months
measure: Rheology: the critical constraint (tau-C).
timeFrame: 12 months
measure: Spirometry: forced expiratory volume in 1 minute (FEV1)
timeFrame: Baseline (day 0)
measure: Spirometry: forced expiratory volume in 1 minute (FEV1)
timeFrame: 3 months
measure: Spirometry: forced expiratory volume in 1 minute (FEV1)
timeFrame: 6 months
measure: Spirometry: forced expiratory volume in 1 minute (FEV1)
timeFrame: 9 months
measure: Spirometry: forced expiratory volume in 1 minute (FEV1)
timeFrame: 12 months
measure: Spirometry: forced vital capacity (FVC)
timeFrame: Baseline (day 0)
measure: Spirometry: forced vital capacity (FVC)
timeFrame: 3 months
measure: Spirometry: forced vital capacity (FVC)
timeFrame: 6 months
measure: Spirometry: forced vital capacity (FVC)
timeFrame: 9 months
measure: Spirometry: forced vital capacity (FVC)
timeFrame: 12 months
measure: Spirometry: FEV1/FVC
timeFrame: Baseline (day 0)
measure: Spirometry: FEV1/FVC
timeFrame: 3 months
measure: Spirometry: FEV1/FVC
timeFrame: 6 months
measure: Spirometry: FEV1/FVC
timeFrame: 9 months
measure: Spirometry: FEV1/FVC
timeFrame: 12 months
measure: Plethysmography for lung volumes: residual volume (RV)
timeFrame: Baseline (day 0)
measure: Plethysmography for lung volumes: residual volume (RV)
timeFrame: 3 months
measure: Plethysmography for lung volumes: residual volume (RV)
timeFrame: 6 months
measure: Plethysmography for lung volumes: residual volume (RV)
timeFrame: 9 months
measure: Plethysmography for lung volumes: residual volume (RV)
timeFrame: 12 months
measure: Plethysmography for lung volumes: functional residual capacity (FRC)
timeFrame: Baseline (day 0)
measure: Plethysmography for lung volumes: functional residual capacity (FRC)
timeFrame: 3 months
measure: Plethysmography for lung volumes: functional residual capacity (FRC)
timeFrame: 6 months
measure: Plethysmography for lung volumes: functional residual capacity (FRC)
timeFrame: 9 months
measure: Plethysmography for lung volumes: functional residual capacity (FRC)
timeFrame: 12 months
measure: Plethysmography for lung volumes: total lung capacity (TLC)
timeFrame: Baseline (day 0)
measure: Plethysmography for lung volumes: total lung capacity (TLC)
timeFrame: 3 months
measure: Plethysmography for lung volumes: total lung capacity (TLC)
timeFrame: 6 months
measure: Plethysmography for lung volumes: total lung capacity (TLC)
timeFrame: 9 months
measure: Plethysmography for lung volumes: total lung capacity (TLC)
timeFrame: 12 months
measure: Plethysmography for lung volumes: RV/TLC
timeFrame: Baseline (day 0)
measure: Plethysmography for lung volumes: RV/TLC
timeFrame: 3 months
measure: Plethysmography for lung volumes: RV/TLC
timeFrame: 6 months
measure: Plethysmography for lung volumes: RV/TLC
timeFrame: 9 months
measure: Plethysmography for lung volumes: RV/TLC
timeFrame: 12 months
measure: Drug consumption throughout the study.
timeFrame: 12 months
measure: The number of adverse events will be recorded throughout the study.
timeFrame: 12 months
measure: Episodes of exacerbation throughout the study
timeFrame: 12 months
measure: Episodes of hospitalization throughout the study
timeFrame: 12 months
measure: Clinical improvement
timeFrame: 12 months
measure: Medical outcomes study 36-Item Short Form Survey (SF-36)
timeFrame: Baseline (day 0)
measure: Medical outcomes study 36-Item Short Form Survey (SF-36)
timeFrame: 3 months
measure: Medical outcomes study 36-Item Short Form Survey (SF-36)
timeFrame: 6 months
measure: Medical outcomes study 36-Item Short Form Survey (SF-36)
timeFrame: 9 months
measure: Medical outcomes study 36-Item Short Form Survey (SF-36)
timeFrame: 12 months
measure: EQ-5D-5L
timeFrame: Baseline (day 0)
measure: EQ-5D-5L
timeFrame: 3 months
measure: EQ-5D-5L
timeFrame: 6 months
measure: EQ-5D-5L
timeFrame: 9 months
measure: EQ-5D-5L
timeFrame: 12 months
measure: St-George's Respiratory Questionnaire
timeFrame: Baseline (day 0)
measure: St-George's Respiratory Questionnaire
timeFrame: 3 months
measure: St-George's Respiratory Questionnaire
timeFrame: 6 months
measure: St-George's Respiratory Questionnaire
timeFrame: 9 months
measure: St-George's Respiratory Questionnaire
timeFrame: 12 months
measure: Blood cell differential: neutrophil levels
timeFrame: Baseline (day 0)
measure: Blood cell differential: eosinophil levels
timeFrame: Baseline (day 0)
measure: Blood cell differential: neutrophil levels
timeFrame: 12 months
measure: Blood cell differential: eosinophil levels
timeFrame: 12 months
measure: Serum Club cell secretory protein
timeFrame: Baseline (day 0)
measure: Serum Club cell secretory protein
timeFrame: 12 months
measure: Sputum bacteriology
timeFrame: Baseline (day 0)
measure: Sputum bacteriology
timeFrame: 12 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: University Hospitals of Bordeaux
city: Montpellier
country: France
facility: University Hospitals of Montpellier
city: Toulouse
country: France
facility: University Hospitals of Toulouse
Study officials:
affiliation: University Hospital, Montpellier
name: Jérémy Charriot, MD
role: STUDY_DIRECTOR
References: