Impact of discontinuation of long-term macrolides in stable Non Cystic Fibrosis Bronchiectasis : a multicenter randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Intercommunal Creteil

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Bacterial Infections and Mycoses [C01]

Decision date (initial)

2026-07-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate the non-inferiority of withdrawal of low-dose macrolides after at least 1 year of treatment, compared to its continuation, in stable NCFB patients.

Secondary objectives 7

1. To compare the 2 arms (withdrawal and continuation) in term of Time to first exacerbation
2. To compare the 2 arms (withdrawal and continuation) in term of Annual number of severe pulmonary exacerbation
3. To compare the 2 arms (withdrawal and continuation) in term of Quality-of-life assessment, at inclusion, 12 and 24 months
4. To compare the 2 arms (withdrawal and continuation) in term of emergence of macrolides-resistant strains of bacteria and mycobacteria
5. To compare the 2 arms (withdrawal and continuation) in term of respiratory symptoms and lung function
6. To compare the 2 arms (withdrawal and continuation) in term of Exploration of prognostic factors for macrolide discontinuation failure
7. To compare the 2 arms (withdrawal and continuation) in term of time to loss of control (defined by the need to start a treatment to prevent exacerbations)

Conditions and MedDRA coding

bronchiectasis unrelated to cystic fibrosis

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. ≥18 years of age, female or male
2. Diagnosis of bronchiectasis on thoracic CT-scan
3. Treatment with long-term Azithromycin for at least 12 months
4. ≤ 1 pulmonary exacerbations in the last 12 months
5. No severe pulmonary exacerbation (with hospitalization due to respiratory failure) in the last 12 months
6. Patient affiliated with the French health care system
7. Able to understand and sign a written informed consent form

Exclusion criteria 16

1. Confirmed diagnosis of cystic fibrosis
2. A primary diagnosis of COPD or asthma as judged by the Investigator. Patients with comorbid COPD and/or asthma can be enrolled if bronchiectasis is their primary diagnosis.
3. Pregnancy or breastfeeding
4. Patient participating to another interventional clinical trial
5. Predictable monitoring issues
6. Long-term oxygen therapy and/or noninvasive mechanical ventilation for chronic respiratory insufficiency (except CPAP for OSA) and/or FEV1<30% of predicted value and/or and/or considered for lung transplantation
7. Contraindication to the use of azithromycin: -allergy to macrolides or ketolides - hypersensitivity to any of the excipients - concomitant treatment with QT-interval–prolonging agents; - electrolyte disturbances (hypokalaemia, hypomagnesaemia); - clinically significant bradycardia, cardiac arrhythmia, or severe heart failure; - renal impairment with creatinine clearance < 40 mL/min - - co-administration with alcaloides de l’ergot de seigle (dihydroergotamine, ergotamin), cisapride and ; colchicine - - QTc is >450 ms for men and >470 ms for women - - Severe liver impairment
8. Severe hemoptysis due to a respiratory cause
9. Patient with a solid tumor or hematologic malignancy receiving active (non-maintenance) treatment.
10. Lung transplantation
11. Allogenic hematopoietic stem cell transplantation
12. Women of childbearing potential * who do not accept the required contraceptive method below.  Combined or progestogen-only hormonal contraception (oral, injectable, implantable, transdermal patch),  Intrauterine device (IUD), including copper or hormone-releasing systems,  Bilateral tubal occlusion/sterilisation,  Complete sexual abstinence, only if it is the participant’s usual and preferred lifestyle and is considered reliable per protocol. * Women are considered not of childbearing potential if they are:Postmenopausal, defined as at least 12 consecutive months of spontaneous amenorrhea without an alternative medical cause, or  Permanently sterilized (e.g., documented hysterectomy, bilateral oophorectomy, or bilateral tubal ligation).
13. Male participants with partners of childbearing potential who do not a accept to use appropriate contraception to prevent pregnancy during the study and for the required follow-up period will be excluded from participation; acceptable contraception methods include: - Male condom; - Vasectomy (with documented medical confirmation of surgical success); - True sexual abstinence, only if this is consistent with the participant’s usual and preferred lifestyle; Double-barrier methods (e.g., condom plus diaphragm/cervical cap/spermicide) may be used, although they are not considered highly effective methods.
14. Patients who are relatives of the investigator or any member of the study team directly involved in the conduct of the study (including physicians, pharmacists, nurses, and study coordinators).
15. Patients deprived of liberty by administrative or judicial decision.
16. Patients under legal protection (guardianship or legal supervision).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the annualized number of PE that have been confirmed through the event adjudication process

Secondary endpoints 7

1. Time (days) to first exacerbation
2. Annual number of severe exacerbations, with hospitalization due to a respiratory failure
3. Quality-of-life score (Quality of Life-Bronchiectasis (QOL-B)16 and Bronchiectasis Impact Measure (BIM)) at inclusion, 1 year and 2 years
4. Emergence of macrolide-resistant strains of bacteria or mycobacteria, at inclusion, 12 and 24 months
5. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), at inclusion, 12 and 24 months
6. Number of days between randomization and a new prescription of preventive treatment for exacerbations (macrolides, anti-inflammatory such as brenzocatib, long-term antibiotic therapy)
7. Prognostic factors for macrolide discontinuation failure (age, severity of the disease, Pseudomonas colonization and duration of macrolides exposition before the beginning of the trial…) will be explored by using uni- and multivariable logistic regression

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Intercommunal Creteil

Sponsor organisation

Centre Hospitalier Intercommunal Creteil

Address

40 Avenue De Verdun

City

Creteil

Postcode

94000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

Benoit Douvry

Public contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

DRSI CHIC

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Results and documents

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

Documents 11 files

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

Application history

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