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

NCT06368804 | Recruiting Phase 2

• 2 other identifiers: ANTEIPA2022-A01575-38
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 18

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.

Conditions

Bronchiectasis

Keywords

Non cystic fibrosis bronchiectasis

Outcome Measures

Primary Outcomes (1)

• PA-eradication rate

  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.

  6 months

Secondary Outcomes (16)

• Time to first exacerbation

  3, 6 and 12 months-follow up visit, or additional visit

• 1 year-exacerbation rate

  3, 6 and 12 months-follow up visit

• Quality-of-life using questionnaires

  Inclusion, 3 and 12 months-follow up visit

• Quality-of-life using questionnaires

  Inclusion, 3 and 12 months-follow up visit

• Treatment burden assessment using questionnaires

  Inclusion, 3 and 12 months-follow up visit

Study Arms (2)

Oral fluoroquinolone + nebulized colistimethate sodium

EXPERIMENTAL

Drug: Antibiotic monotherapy treatment and follow-up

IV beta-lactam antibiotic (ceftazidime) + oral fluoroquinolone + nebulized colistimethate sodium

ACTIVE COMPARATOR

Drug: Antibiotic bitherapy treatment and follow-up

Interventions

Antibiotic monotherapy treatment and follow-up DRUG

1. a 3-months treatment period, including: * an initial phase of 14 days, combining an oral fluoroquinolone (ciprofloxacin 750mg tw/d) with nebulized sodium colistimethate (1 Million Units tw/d) * a maintenance phase of 2.5 months: nebulized sodium colistimethate (1 MU tw/d) ; 2. a subsequent follow-up period of 9 months (i.e. until 12 months after the start of antibiotic therapy against Pseudomonas aeruginosa).

Oral fluoroquinolone + nebulized colistimethate sodium

Antibiotic bitherapy treatment and follow-up DRUG

1. a 3-months treatment period, including: * an initial phase of 14 days, combining an IV beta-lactam antibitic (ceftazidime 4 or 6g/d) and an oral fluoroquinolone (ciprofloxacin 750mg tw/d) with nebulized sodium colistimethate (1 Million Units tw/d) * a maintenance phase of 2.5 months: nebulized sodium colistimethate (1 MU tw/d) ; 2. a subsequent follow-up period of 9 months (i.e. until 12 months after the start of antibiotic therapy against Pseudomonas aeruginosa).

IV beta-lactam antibiotic (ceftazidime) + oral fluoroquinolone + nebulized colistimethate sodium

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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

You may not qualify if:

• 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
• Severe chronic renal failure defined by a creatinine clearance (Cockcroft or MDRD) ≤ 30 mL/min/1.73m2 or chronic haemodialysis
• Severe hepatic impairment

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead
• Assistance Publique - Hôpitaux de Paris: collaborator

Study Sites (18)

CHU Amiens-Picardie

Amiens, France

RECRUITING

CHU Haut Leveque, Bordeaux

Bordeaux, France

RECRUITING

CHRU Brest

Brest, France

RECRUITING

CH Pontoise

Cergy-Pontoise, France

RECRUITING

Centre hospitalier intercommunal de Créteil

Créteil, 94010, France

RECRUITING

APHP, Henri Mondor

Créteil, France

RECRUITING

Hôpital de la Croix Rousse, HCL, Lyon

Lyon, France

NOT YET RECRUITING

Clinique St Joseph

Marseille, 13008, France

RECRUITING

CHU Nantes

Nantes, France

RECRUITING

CHU H. Pasteur, Nice

Nice, France

NOT YET RECRUITING

Hôpital Pitié Salpêtrière

Paris, 75013, France

RECRUITING

APHP, Cochin

Paris, France

RECRUITING

APHP, Saint Louis

Paris, France

RECRUITING

APHP, Tenon

Paris, France

RECRUITING

Hôpital Foch, Suresnes

Suresnes, France

RECRUITING

CHU H. Larrey, Toulouse

Toulouse, France

RECRUITING

CH Versailles

Versailles, France

RECRUITING

CH Villefranche s/Saône

Villefranche-sur-Saône, France

RECRUITING

MeSH Terms

Conditions

Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Central Study Contacts

Camille JUNG, MD

CONTACT

0157022000; camille.jung@chicreteil.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: April 16, 2024
• Study Start: September 15, 2024
• Primary Completion: March 15, 2025
• Study Completion (Estimated): September 15, 2028
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)