Comparison of Two Antibiotic Regimens for the Treatment of Early Airways Infection With PA in Adults With Bronchiectasis

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

Trial duration

21 Oct 2024 → ongoing

Decision date (initial)

2024-02-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Direction générale de l'Offre de soins (DGOS)

External identifiers

EU CT number

2023-504755-26-00

ClinicalTrials.gov

NCT06368804

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate the non-inferiority of 14-day oral ciprofloxacin immediately combined with nebulized colistimethate sodium (colistin) for 3 months over 14-day systemic dual therapy (including an IV anti-PA beta-lactam) combined with nebulized colistimethate sodium (colistin) for 3 months on the 6-month PA eradication rate of early PA infection in patients with bronchial dilatation disease (BDD)

Secondary objectives 5

1. Compare the 2 treatment arms in terms of clinical efficacy (time to first exacerbation, exacerbation rate at 1 year, quality of life assessed at 3 months and 1 year)
2. Compare the 2 treatment arms in terms of microbiological efficacy (detection of AP at 3 months and 1 year, time to first recurrence of AP)
3. Compare the 2 treatment arms, in terms of treatment safety (premature discontinuation of one of the study treatments due to any adverse event, serious and non-serious adverse events and their causal relationship to one of the study treatments, emergence of FQ-resistant strains of AP or other bacteria)
4. Compare the 2 treatment arms, in terms of treatment adherence (premature discontinuation of one of the study treatments, proportion of unadministered doses of nebulized colistin)
5. Compare the 2 therapeutic arms in terms of medico-economic impact (cost and incremental cost-effectiveness ratio at 1 year)

Conditions and MedDRA coding

Bronchiectasis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. ≥18 years of age
2. Diagnosis of bronchiectasis on thoracic CT-scan
3. Isolation of PA in a respiratory sample (spontaneous or induced sputum or other lower respiratory tract sample obtained by bronchoscopy) taken no more than 3 months prior to randomisation, and if this sample was taken more than 4 weeks (28 days) prior to the planned randomisation date, a new respiratory sample must have been taken and confirmed the persistence of PA prior to randomisation.
4. Patient either Pseudomonas naive (i.e., never previously isolated PA) or Pseudomonas free (i.e., infection-free for ≥1 year, proven by at least two PA negative respiratory sample during the last year)
5. Patient affiliated with the French health care system
6. Able to understand and sign a written informed consent form

Exclusion criteria 20

1. Confirmed diagnosis of cystic fibrosis
2. Severe exacerbation requiring admission to an intensive care unit (e.g. for non-invasive ventilatory support, invasive mechanical ventilation, catecholamine or any other organ supportive therapy)
3. Prior severe reaction, hypersensitivity reaction or other contraindication to any of the treatments in study (ciprofloxacin, beta-lactam, colistimethate sodium)
4. Prior severe bronchospasm attributed to a nebulization
5. Patients already receiving PA suppressive therapy with an inhaled antibiotic (long-term azithromycin therapy accepted)
6. Prior PA-eradication antibiotic treatment (systemic antibiotic(s) active against PA for ≥ 14 days or nebulized anti-PA antibiotic) within the last year
7. Antibiotic treatment active against PA (anti-PA beta-lactam antibiotic and/or FQ and/or aminoglycoside) for more than 3 days before randomisation
8. Protected person (pregnant woman, nursing mother, person under guardianship, minor, person deprived of liberty, person unable to give consent)
9. Patient who has already taken part in the ANTEIPA study
10. Active cancer or haematological malignancy under active therapy
11. Systemic corticosteroid therapy ≥ 20 mg/d. prednisone equivalent for a predictable duration > 4 weeks
12. Non-tuberculous mycobacterial infection or positive non-tuberculous mycobacterial respiratory specimen within 1 year prior to inclusion
13. Severe chronic renal failure defined by a creatinine clearance (Cockcroft or MDRD) ≤ 30 mL/min/1.73m2 or chronic haemodialysis
14. Long-term oxygen therapy and/or noninvasive mechanical ventilation for chronic respiratory insufficiency (except continuous positive airway pressure for OSA) and/or forced expiratory volume at one second (FEV1) <25% of predicted value
15. Patient participating to another interventional clinical trial
16. Pregnancy or breastfeeding
17. P. aeruginosa resistant to ciprofloxacin or ceftazidime
18. Women of childbearing potential (following menarche and until becoming post-menopausal unless permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy)) who refuse to use effective contraception (hormonal or mechanical) for 3 months and/or to undergo pregnancy tests at baseline, 1 month and 3 months after baseline
19. Isolation of P.Aeruginosa (PA) in a respiratory specimen (spontaneous or induced sputum or other lower respiratory tract specimen obtained by bronchoscopy) more than 3 months to 12 months prior to randomization
20. Acute liver failure

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PA-eradication rate 6 months after the start of antibiotic therapy targeting PA

Secondary endpoints 11

1. Exacerbation assessment at each follow-up visit, with time (in days) between the start of antibiotic therapy against PA and first exacerbation
2. Exacerbation assessment at each follow-up visit
3. Quality-of-life and treatment burden assessment using questionnaires, Quality of Life-Bronchiectasis (QOL-B), Bronchiectasis Impact Measure (BIM), Treatment Burden Questionnaire (TBQ) (+ EQ-5D-5L questionnaire for the medico-economic analysis)
4. Detection of PA at 3-month and 1 year
5. PA-recurrence in sputum (or lower respiratory tract sample, if clinically justified), with time (in days) between the start of antibiotic therapy against PA and first PA-recurrence
6. Analysis of PA (or other bacteria) susceptibility to ciprofloxacin, if growing on respiratory sample(s) performed between 3 months and 12 months
7. AE and serious AEs will be recorded during medical interviews and by self-report in the study booklet up to 4 months after the start of treatment
8. Number of premature ending of one of the treatment in study due to any AE. Compliance to treatment and AEs will be recorded during medical interviews and by self-report in the study booklet during the study treatment period, time (in days)
9. Number of premature ending of one of the treatment in study. Compliance to treatment will be recorded during medical interviews and by self-report in the study booklet during the study treatment period, time (in days)
10. Proportion of non-administered doses of nebulized colistin.Compliance to treatment will be recorded during medical interviews and by self-report in the study booklet during the study treatment period, time (in days)
11. Total cost in each group, total quality adjusted life years (QALYs) in each group, difference in costs /difference in QALYs

Investigational products

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

Test 3

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

Pr MAITRE Bernard

Public contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

Pr MAITRE Bernard

Locations

1 EU/EEA country · 22 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

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