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

Phase 2

Recruiting

• Conditions: Bronchiectasis
• Interventions: Drug: Antibiotic bitherapy treatment and follow-up; Drug: Antibiotic monotherapy treatment and follow-up

• Registration Number: NCT06368804
• Lead Sponsor: Centre Hospitalier Intercommunal Creteil

Brief Summary

Chronic airways infection with Pseudomonas aeruginosa (PA) is associated with increased frequency of exacerbations, deterioration in quality of life and increased mortality in adult patients with bronchiectasis. Current guidelines suggest the prescription of an eradication antibiotic treatment for a first episode of PA infection (early PA infection). Several antibiotic regimens may be proposed, ranging from a monotherapy with oral fluoroquinolone (FQ) to an intravenous cotherapy with the addition of inhaled antibiotics that seems to improve the rate of PA eradication. As no study strictly favoured one regimen, current practices are heterogeneous and could certainly benefit from stronger evidence, with both medical and economic impact.

Detailed Description

According to current knowledge, the early combination of an oral FQ to an inhaled antibiotic could be an acceptable alternative to a systemic cotherapy. Indeed, such regimen allows avoiding IV drugs use, facilitating ambulatory management and influencing patient's quality of life and costs, and may achieve similar PA-eradication rate.

Study Timeline

• Study First Submitted: 2024-02-22
• Study First Submitted QC: 2024-04-11
• Study First Posted: 2024-04-16
• Study Start: 2024-09-15
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-13
• Last Update Posted: 2025-02-14
• Primary Completion: 2025-03-15
• Study Completion: 2028-09-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 196

Inclusion Criteria

• ≥18 years of age
• Diagnosis of bronchiectasis on thoracic CT-scan
• Recent isolation of P. aeruginosa (PA) in a respiratory sample (spontaneous or induced sputum or other lower respiratory tract sample obtained by bronchoscopy) within the last 3 months, with a PA positive respiratory sample obtained ≤ 3 weeks before randomization
• 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)
• Patient affiliated with the French health care system
• Able to understand and sign a written informed consent form

Exclusion Criteria

• Confirmed diagnosis of cystic fibrosis
• Pregnancy or breastfeeding
• Women of childbearing potential (after the first menstrual period and until menopause or permanent sterility (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.
• Isolation of 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.
• PA resistant to ciprofloxacin or ceftazidime
• 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)
• Prior severe reaction, hypersensitivity reaction or other contraindication to any of the treatments in study (ciprofloxacin, beta-lactam, colistimethate sodium)
• Prior severe bronchospasm attributed to a nebulization
• Patients already receiving PA suppressive therapy with an inhaled antibiotic (long-term azithromycin therapy accepted)
• Prior PA-eradication antibiotic treatment (systemic antibiotic(s) active against PA for ≥ 14 days or nebulized anti-PA antibiotic) within the last year
• Antibiotic treatment active against PA (anti-PA beta-lactam antibiotic and/or FQ and/or aminoglycoside) for more than 3 days before randomisation
• Active cancer or haematological malignancy under active therapy
• Systemic corticosteroid therapy ≥ 20 mg/d. prednisone equivalent for a predictable duration > 4 weeks
• Non-tuberculous mycobacterial infection or positive non-tuberculous mycobacterial respiratory specimen within 1 year prior to inclusion
• Severe chronic renal failure defined by a creatinine clearance (Cockcroft or MDRD) ≤ 30 mL/min/1.73m2 or chronic haemodialysis
• Severe hepatic impairment
• 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.
• Patient participating to another interventional clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV beta-lactam antibiotic (ceftazidime) + oral fluoroquinolone + nebulized colistimethate sodium	Antibiotic bitherapy treatment and follow-up	-
Oral fluoroquinolone + nebulized colistimethate sodium	Antibiotic monotherapy treatment and follow-up	-

Primary Outcome Measures

Name	Time	Method
PA-eradication rate	6 months	PA-eradication rate 6 months after the start of antibiotic therapy targeting PA, where PA eradication is defined as follows: * Sputum culture (or lower airway specimen culture, if respiratory exacerbation\* with inability to perform good quality sputum analysis) negative for PA at the 6-month follow-up visit, or; * Inability to spit in the absence of a pulmonary exacerbation\*, AND; * No sputum culture or lower airway specimen positive for PA between D90 of antibiotic treatment and the 6-month follow-up visit, in the absence of new antibiotic therapy targeting PA.

Secondary Outcome Measures

Name	Time	Method
1 year-exacerbation rate	3, 6 and 12 months-follow up visit	exacerbation assessment at each follow-up visit
Time to first PA-recurrence	3, 6 and 12 months-follow up visit	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
Time to first exacerbation	3, 6 and 12 months-follow up visit, or additional visit	exacerbation assessment at each follow-up visit, with time (in days) between the start of antibiotic therapy against PA and first exacerbation
Quality-of-life using questionnaires	Inclusion, 3 and 12 months-follow up visit	EQ-5D-5L questionnaire for the medico-economic analysis
Treatment burden assessment using questionnaires	Inclusion, 3 and 12 months-follow up visit	Treatment Burden Questionnaire (TBQ)
Number of premature ending of one of the treatment in study due to any AE	1 months and 3 months-follow up visit	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)
Number of premature ending of one of the treatment in study	1 months and 3 months-follow up visit	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)
Cost and incremental cost effectiveness ratio at 1 year	Inclusion and each follow up visit up to one year for quality of life measures; initial discharge and subsequent exacerbation-related readmissions up to one year.	Difference in costs /difference in QALYs
Detection of PA at 3-month and 1 year	3 and 12 months-follow up visit	Sputum (or lower respiratory tract sample, if clinically justified) culture growing PA
Emergence of FQ-resistant strains of (PA or other bacteria)	3, 6 and 12 months-follow up visit	analysis of PA (or other bacteria) susceptibility to ciprofloxacin, if growing on respiratory sample(s) performed between 3 months and 12 months
Adverse event (AE) and serious AE at 12 months follow-up	during the 12 months follow-up	AE and serious AEs will be recorded during medical interviews and by self-report in the study booklet during the study
Proportion of non-administered doses of nebulized colistin	1 months and 3 months-follow up visit	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)

Trial Locations

Locations (18)

CHU Amiens-Picardie; 🇫🇷 Amiens, France

CHU Haut Leveque, Bordeaux; 🇫🇷 Bordeaux, France

CHRU Brest; 🇫🇷 Brest, France

CH Pontoise; 🇫🇷 Cergy-Pontoise, France

Centre hospitalier intercommunal de Créteil; 🇫🇷 Créteil, France

APHP, Henri Mondor; 🇫🇷 Créteil, France

Hôpital de la Croix Rousse, HCL, Lyon; 🇫🇷 Lyon, France

Clinique St Joseph; 🇫🇷 Marseille, France

CHU Nantes; 🇫🇷 Nantes, France

CHU H. Pasteur, Nice; 🇫🇷 Nice, France

Hôpital Pitié Salpêtrière; 🇫🇷 Paris, France

APHP, Cochin; 🇫🇷 Paris, France

APHP, Saint Louis; 🇫🇷 Paris, France

APHP, Tenon; 🇫🇷 Paris, France

Hôpital Foch, Suresnes; 🇫🇷 Suresnes, France

CHU H. Larrey, Toulouse; 🇫🇷 Toulouse, France

CH Versailles; 🇫🇷 Versailles, France

CH Villefranche s/Saône; 🇫🇷 Villefranche-sur-Saône, France