Comparison of 2 Treatment Regimens for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis

Study Overview
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Brief Summary
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Treatment of new Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) can postpone chronic infection. Aim of the study: compare 2 Pa eradication regimens in children with new Pa infection.

Detailed Description
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Methods: CF children (0-18 years) with a new isolation of Pa from the airway were randomized to tobramycin inhalation solution (TOBI® 2x300 mg for 28 days) (TIS) or inhaled colistimethate sodium (Colistineb® 2x2 mill U daily) plus oral ciprofloxacin (30mg/kg/day) for 3 months (CC). The primary outcome was eradication at end of treatment. Secondary outcome parameters were time to Pa relapse, total and Pa specific IgG, FEV1, BMI and Pa status.

Official Title
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Prospective Randomized Trial Comparing Oral Ciproxin Plus Inhaled Colistin With Tobramycin for Inhalation for Eradication of P Aeruginosa Infection in Children With Cystic Fibrosis.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: oral ciprofloxacin plus inhaled colistin
* Drug: TOBI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of CF (clinical signs consistent with CF and a sweat chloride > 60 mEq/l by quantitative pilocarpine iontophoresis and/or two CF causing mutations identified) age 0 to 18 years old at time of inclusion 'First' or 'new Pa infection' defined as 'first Pa isolation ever' or 'isolation of Pa from the airway (sputum, throat swab or BAL) after a Pa free interval of at least 6 months and documented with at least 3 negative cultures'. Exclusion Criteria: chronic Pa infection defined according to the Leeds criteria[17] pulmonary exacerbation needing IV AB treatment at time of new Pa isolate Pa isolation at time of CF diagnosis patient already on an antipseudomonal antibiotic interval between positive culture and start of treatment > 4 weeks.

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ciproxin-inhaled Colistin<br>oral ciprofloxacin (30mg/kg/day) plus inhaled colistimethate sodium (Colistineb® 2x2 mill U daily) for 3 months | Drug: oral ciprofloxacin plus inhaled colistin<br>* oral ciprofloxacin (30mg/kg/day divided in 2 doses) for 3 months (CC) plus inhaled colistimethate sodium(Colistineb® 2x2 mill U daily)<br>* Other names: Colistineb ®;|
| Active Comparator: Tobramycine for inhalation (TIS)<br>tobramycin inhalation solution (TOBI® 2x300 mg) for 28 days | Drug: TOBI<br>* tobramycin inhalation solution (TOBI® 2x300 mg) for 28 days<br>* Other names: TOBI® - tobramycin inhalation solution (TIS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pseudomonas aeruginosa eradication at the end of the treatment. | sucessful eradication is defined as negative airway culture for P aeruginosa and end of study drug which is after 3 months for ciproxin-colistin (CC) and after 1 months for tobramycin for inhalation (TIS) | end of study drug treatment ie 3 months for CC and at 1 months for TIS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P aeruginosa eradication at 6 months after study entry | negative airway cultures for P aeruginosa up to 6 months after start of study drug | 6 months | 
| time to new Pa positive culture (= relapse) | Time to first new P aeruginosa positive airway culture (expressed in months starting from end of study drug) | 1 year | 
| change from baseline FEV1% pred, IgG z score, BMI z score was followed | Evolution of lung function (expressed as FEV1% pred), total IgG and nutritional status (expressed as BMI z score) from start of study up to 1 year | 1 year | 
| Antibody titer for specific anti Pseudomonas antibodies | Pa antibodies (ELISA St Ag 1-17 )were measured at baseline and at 1 year follow-up | 1 year | 
| P aeruginosa infection status | P aeruginosa infection status was reported as 'Free off', 'Intermittent' or 'Chronic' according to the Leeds criteria after 1 and 2 years. (ref Leeds criteria: Lee TW, Brownlee KG, Conway SP, et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003;2(1):29-34) | 1 year | 
| P aeruginosa infection status | P aeruginosa infection status was reported as 'Free off', 'Intermittent' or 'Chronic' according to the Leeds criteria after 1 and 2 years. (ref Leeds criteria: Lee TW, Brownlee KG, Conway SP, et al. Evaluation of a new definition for chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. J Cyst Fibros 2003;2(1):29-34) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis- P aeruginosa- eradication-child