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

Bronchiectasis Clinical Trial

— ANTEIPA  

Official title:

Comparison of Two Antibiotic Regimens for the Treatment of Early Airways Infection With Pseudomonas Aeruginosa in Adults With Bronchiectasis: a Non-inferiority Randomized Controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06368804
• Other study ID #: ANTEIPA
• Secondary ID: 2022-A01575-38
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2024
• Est. completion date: June 1, 2028

Study information

• Verified date: April 2024
• Source: Centre Hospitalier Intercommunal Creteil
• Contact: Camille JUNG
• Phone: 0157022268
• Email: camille.jung[@]chicreteil.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 196
• Est. completion date: June 1, 2028
• Est. primary completion date: November 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• Antibiotic monotherapy treatment and follow-up
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) ; a subsequent follow-up period of 9 months (i.e. until 12 months after the start of antibiotic therapy against Pseudomonas aeruginosa).
• Antibiotic bitherapy treatment and follow-up
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) ; a subsequent follow-up period of 9 months (i.e. until 12 months after the start of antibiotic therapy against Pseudomonas aeruginosa).

Locations

Country	Name	City	State
France	CHU Amiens-Picardie	Amiens
France	CHU Haut Leveque, Bordeaux	Bordeaux
France	CHRU Brest	Brest
France	CH Pontoise	Cergy-Pontoise
France	APHP, Henri Mondor	Créteil
France	Centre hospitalier intercommunal de Créteil	Créteil
France	Hôpital de la Croix Rousse, HCL, Lyon	Lyon
France	CHU Nantes	Nantes
France	CHU H. Pasteur, Nice	Nice
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

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal Creteil	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	3, 6 and 12 months-follow up visit, or additional visit
Secondary	1 year-exacerbation rate	exacerbation assessment at each follow-up visit	3, 6 and 12 months-follow up visit
Secondary	Quality-of-life using questionnaires	Quality of Life-Bronchiectasis (QOL-B)	Inclusion, 3 and 12 months-follow up visit
Secondary	Quality-of-life using questionnaires	Bronchiectasis Impact Measure (BIM)	Inclusion, 3 and 12 months-follow up visit
Secondary	Treatment burden assessment using questionnaires	Treatment Burden Questionnaire (TBQ)	Inclusion, 3 and 12 months-follow up visit
Secondary	Quality-of-life using questionnaires	EQ-5D-5L questionnaire for the medico-economic analysis	Inclusion, 3 and 12 months-follow up visit
Secondary	Detection of PA at 3-month and 1 year	Sputum (or lower respiratory tract sample, if clinically justified) culture growing PA	3 and 12 months-follow up visit
Secondary	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	3, 6 and 12 months-follow up visit
Secondary	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	3, 6 and 12 months-follow up visit
Secondary	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	during the 12 months follow-up
Secondary	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)	1 months and 3 months-follow up visit
Secondary	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)	1 months and 3 months-follow up visit
Secondary	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)	1 months and 3 months-follow up visit
Secondary	Cost and incremental cost effectiveness ratio at 1 year	Total cost in each group	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.
Secondary	Cost and incremental cost effectiveness ratio at 1 year	Total quality adjusted life years (QALYs) in each group	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.
Secondary	Cost and incremental cost effectiveness ratio at 1 year	Difference in costs /difference in QALYs	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.