COPD-CARhE - Chronic Airway Disease, Mucus Rheology and Exacerbations: a clinical Trial of COPD Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

3 Feb 2023 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS - GIRCI-SOHO ”Programme Hospitalier de Recherche Clinique Inter-Régional

External identifiers

EU CT number

2024-516172-15-00

EudraCT number

2019-004182-41

ClinicalTrials.gov

NCT04669270

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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.

Secondary objectives 8

1. To compare between the two arms, the exacerbation number according to their severity (observed throughout the duration of the study)
2. To compare between the two arms, the evolution of the symptoms, the rheology of the sputum, and the pulmonary function (measurements repeated every three months)
3. To compare between the two arms, medication consumption and adverse events (monitored throughout the duration of the study)
4. To compare between the two arms, patient trajectories during follow-up
5. To compare between the two arms, the overall clinical improvement at the end of the study and the evolution of the quality of life (measurements repeated every 3 months)
6. To compare between the two arms, the change in biomarkers of interest (baseline versus end of study)
7. Compare the exacerbation number between the experimental arm without azithromycin prescription and the comparator arm without azithromycin, and between the experimental arm with azithromycin prescription and the comparator arm with azithromycin.
8. Estimate the rate of patients in the experimental arm who would have had different care using CASA-Q versus rheology.

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Subjets between 40 - 85 years (included)
2. Written and signed informed consent form
3. Subjects must be able to attend all planned visits and comply with all test procedures
4. Beneficiary of or affiliated with the French social security system
5. 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
6. Spontaneous or induced sputum production
7. Electrocardiogram: corrected distance between Q and T waves (QTC) <450 ms in men, QTC <470 ms in women
8. Normal audiogram for age or absence of contraindication to azithromycin for long course according to Oto-Rhino-Laryngological specialist opinion

Exclusion criteria 13

1. Pregnancy or breastfeeding
2. Patients who are prisoners or other forms of judicial protection
3. Patients under any form of tutorship / curatorship
4. The patient participates in another interventional protocol, or did so in the month prior to inclusion
5. Received azithromycin in the previous 3 months
6. Patient whose primary diagnosis is bronchial dilation based on CT scan documentation
7. Known hypersensitivity to azithromycin, erythromycin, any other macrolide, ketolide or any of the excipients of the azithromycin-based specialty used
8. Concomitant use of medication contraindicated with azithromycin (dihydroergotamine, ergotamine, cisapride, colchicine)
9. Other respiratory diseases or associated lung infections
10. Severe hepatic insufficiency and severe cholestasis (a liver biological test will be carried out if clinical suspicion)
11. Renal impairment with creatinine clearance < 40 mL/min
12. Patients with hematological malignancies who have undergone allogeneic hematopoietic stem cell transplantation
13. Patients with conditions contraindicating the use of an azithromycinbased product due to its composition in excipient with a notable effect. For example, in the presence of lactose, patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary disease) . See the information available on the Public Drug Database, accessible on the Internet at the following address: http://base-donnees-publique.medicaments.gouv.fr

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The number of exacerbations over the 12 months of follow-up

Secondary endpoints 29

1. The number of mild exacerbations throughout follow-up. A mild exacerbation does not require new additional medicine
2. The number of moderate exacerbations throughout follow-up. Moderate exacerbations require antibiotics or oral corticosteroids (but not hospitalization)
3. The number of severe exacerbations throughout follow-up. Severe exacerbations require hospitalization
4. Comparison on the evolution of symptoms assessed by the COPD Assessment Test (CAT) questionnaire score at 3 months, 6 months, 9 months and 12 months
5. Comparison on the evolution of symptoms assessed by the score of the Cough and sputum assessment questionnaire (CASA-Q) questionnaire score at 3 months, 6 months, 9 months and 12 months
6. Comparison on the evolution of symptoms assessed by the score of the Visual analogue scale (VAS) score for dyspnea, coughing and sputum production at 3 months, 6 months, 9 months and 12 months
7. Comparison on sputum rheology (modulus of elasticity of mucus, parameter G' ) measured using the Rheomuco device at 3 months, 6 months, 9 months and 12 months
8. Comparison on sputum rheology (viscous module, parameter G'') measured using the Rheomuco device at 3 months, 6 months, 9 months and 12 months
9. Comparison on sputum rheology (ratio G ''/G ') measured using the Rheomuco device at 3 months, 6 months, 9 months and 12 months
10. Comparison on sputum rheology (critical constraint, parameter tau-C) measured using the Rheomuco device at 3 months, 6 months, 9 months and 12 months
11. Comparison on pulmonary function (forced expiratory volume in 1 s, FEV1) measured by Spirometry at 3 months, 6 months, 9 months and 12 months
12. Comparison on pulmonary function (forced vital capacity, FVC) measured by Spirometry at 3 months, 6 months, 9 months and 12 months
13. Comparison on pulmonary function (FEV1/FVC ratio) measured by Spirometry at 3 months, 6 months, 9 months and 12 months
14. Comparison on pulmonary function (residual volume, RV) measured by Plethysmography at baseline and 12 months
15. Comparison on pulmonary function (functional residual capacity, FRC) measured by Plethysmography at baseline and 12 months
16. Comparison on pulmonary function (total lung capacity, TLC) measured by Plethysmography at baseline and 12 months
17. Comparison on pulmonary function (ratio RV/TLC) measured by Plethysmography at baseline and 12 months
18. Comparison on drug consumption throughout follow-up
19. Number of adverse events throughout follow-up
20. Comparison on number of days with exacerbations and associated symptoms / treatments throughout follow-up
21. Comparison on number of days of hospitalizations and associated symptoms / treatments throughout follow-up
22. Clinical improvement comparison scored via a point system from 0 to 3 at the end of the study (1 point: no more than one exacerbation without hospitalization during the 52 weeks of follow-up; 1 point: gain > 100mL in pre-bronchodilator FEV1 at the 52nd week compared to the baseline state; 1 point: variation of the CAT score during the 52 weeks of observation > 2)
23. Comparison on the evolution of quality of life by the score of the EQ-5D-5L questionnaire score at 3 months, 6 months, 9 months and 12 months
24. Comparison on the evolution of quality of life by the score of the St-George’s Respiratory questionnaire score at 3 months, 6 months, 9 months and 12 months
25. Change in complete blood counts, including neutrophils, eosinophils between baseline and the end of the study
26. Change in level of Serum Club cell secretory protein between baseline and the end of the study
27. Comparison on number of exacerbations between the experimental and comparator arms without prescription of azithromycin
28. Comparison on number of exacerbations between the experimental and comparator arms with prescription of azithromycin
29. Assessment of Azithromycin prescription according to CASA-Q in the experimental arm

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

191 Avenue Du Doyen Gaston Giraud

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Jérémy CHARRIOT

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

Jérémy CHARRIOT

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications