Evaluation of Short Antibiotic Combination Courses Followed by Aerosols in Cystic Fibrosis

Study Overview
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Brief Summary
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The aim of this study is to investigate the efficacy of antibiotic therapy with any antibiotic (IV) and IV (Nebcin®) tobramycin for 5 days followed by Solution for nebuliser inhalation (Tobi®) for 9 days and antibiotic cures using 14 days of tobramycin IV. In the case of positive results, the reduction of the duration of IV treatment of tobramycin from 14 days to 5 days would limit the risk of toxicity.

Official Title
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Evaluation of an Antibiotic Treatment With 14 Days of Intravenous Tobramycin Versus the Same Antibiotic Associated With 5 Days of Intravenous Tobramycin Followed by Tobramycin Aerosol for 9 Days in Cystic Fibrosis.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Tobi Inhalant Product
* Drug: Nebcin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with cystic fibrosis confirmed by sweat or genetic test Patient with clinical signs of exacerbation (increased cough, sputum (abundance, purulence), fever, anorexia, weight loss and FEV1) or acute exacerbations (defined at the clinician's discretion ) FEV1 ≥ 25% Pseudomonas aeruginosa chronic carriers (defined by at least two antipyocyanic precipitation arcs or at least 3 successive positive ECBCs over a period of 18 months) Patient who received at least 1 IV course of antibiotics in the 18 months prior to inclusion. Exclusion Criteria: Severe exacerbation (requiring hospitalization due to severe amputation of FEV 1, oxygen deficiency, or severe impairment of general health). Patient with 3rd antibiotic therapy (triple therapy) Patient colonized in Burkholderia cepacia Patient colonized by an atypical mycobacterium Patient with pulmonary transplant or transplant chronic tinnitus patient using hearing aid Hypersensitivity to tobramycin and other antibiotics of the aminoglycoside family Cirrhosis of Grades B and C according to the Child-Pugh Classification Myasthenia gravis Simultaneous administration of another aminoglycoside Renal failure Recent history of severe hemoptysis (within 2 months before inclusion) Patient participating simultaneously in another clinical study conducted on a drug for the duration of its participation in this research

Ages Eligible for Study
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Minimum Age: 8 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard cure<br>Antibiotic IV (Nebcin) 14 days and 14 days of tobramycin IV associated with one or more other antibiotic (s) IV in routine care | Drug: Tobi Inhalant Product<br>* inhaled tobramycin 300 mg twice per day<br>Drug: Nebcin<br>* 10 to 12 mg/kg/day in 1 injection for adults and 10 to 15 mg/kg in 1 pediatric injection (combined with another IV antibiotic)<br>|
| Experimental: Short cure<br>antibiotic IV (Nebcin)14 days but with only 5 days of tobramycin IV followed 9 days of inhaled tobramycin (Tobi Inhalant Product) associated with one or more other antibiotic (s) IV in routine care | Drug: Tobi Inhalant Product<br>* inhaled tobramycin 300 mg twice per day<br>Drug: Nebcin<br>* 10 to 12 mg/kg/day in 1 injection for adults and 10 to 15 mg/kg in 1 pediatric injection (combined with another IV antibiotic)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume at one second (FEV1) by spirometry | measure of dyspnea | 18 months of the cure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume at one second (FEV1) by spirometry | measure of dyspnea | baseline and between day 16 or day 22 | 
| Visual Analog Scale | measure of dyspnea, condition of patient, bronchial congestion | baseline and between day 16 or day 22 | 
| number of participants with Bronchial congestion |  | baseline and between day 16 or day 22 | 
| Sputum sample culture | a descriptive analysis of Pseudomonas aeruginosa, and the other bacteria in the bacterial flora of sputum | baseline and between day 16 or day 22 | 
| Occurrence of the first exacerbation after the cure |  | during 18 months | 
| Number of pulmonary exacerbations and those leading to hospitalization |  | during 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis, tobramycin, antibiotic courses, FEV1