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

Phase 2RecruitingNCT06368804

Centre Hospitalier Intercommunal Creteil196 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

196

Conditions

Bronchiectasis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (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, France

RECRUITING

APHP, Henri Mondor

Créteil, France

RECRUITING

Hôpital de la Croix Rousse, HCL, Lyon

Lyon, France

NOT_YET_RECRUITING

Clinique St Joseph

Marseille, France

RECRUITING

CHU Nantes

Nantes, France

RECRUITING

CHU H. Pasteur, Nice

Nice, France

NOT_YET_RECRUITING

...and 8 more locations

Outcomes

Primary Outcomes

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.

Time frame: 6 months

Secondary Outcomes

Time to first exacerbation

exacerbation assessment at each follow-up visit, with time (in days) between the start of antibiotic therapy against PA and first exacerbation

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

1 year-exacerbation rate

exacerbation assessment at each follow-up visit

Time frame: 3, 6 and 12 months-follow up visit

Quality-of-life using questionnaires

Quality of Life-Bronchiectasis (QOL-B)

Time frame: Inclusion, 3 and 12 months-follow up visit

Quality-of-life using questionnaires

Bronchiectasis Impact Measure (BIM)

Time frame: Inclusion, 3 and 12 months-follow up visit

Treatment burden assessment using questionnaires

Treatment Burden Questionnaire (TBQ)

Time frame: Inclusion, 3 and 12 months-follow up visit

Quality-of-life using questionnaires

EQ-5D-5L questionnaire for the medico-economic analysis

Time frame: Inclusion, 3 and 12 months-follow up visit

Detection of PA at 3-month and 1 year

Sputum (or lower respiratory tract sample, if clinically justified) culture growing PA

Time frame: 3 and 12 months-follow up visit

Time to first PA-recurrence

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 frame: 3, 6 and 12 months-follow up visit

Emergence of FQ-resistant strains of (PA or other bacteria)

analysis of PA (or other bacteria) susceptibility to ciprofloxacin, if growing on respiratory sample(s) performed between 3 months and 12 months

Time frame: 3, 6 and 12 months-follow up visit

Adverse event (AE) and serious AE at 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

Time frame: during the 12 months follow-up

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)

Time frame: 1 months and 3 months-follow up visit

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)

Time frame: 1 months and 3 months-follow up visit

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)

Time frame: 1 months and 3 months-follow up visit

Cost and incremental cost effectiveness ratio at 1 year

Total cost in each group

Time frame: 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.

Cost and incremental cost effectiveness ratio at 1 year

Total quality adjusted life years (QALYs) in each group

Time frame: 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.

Cost and incremental cost effectiveness ratio at 1 year

Difference in costs /difference in QALYs

Time frame: 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.

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

Overview

Conditions

Interventions

Eligibility

Locations (18)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts