NCT02888730.

Study name	Efficacy of Antibiotic (Tobramycin) Delivered by Nebulized Sonic Aerosol for Chronic Rhinosinusitis Treatment of Cystic Fibrosis Patients: A Multicenter Double‐blind Randomized Controlled Trial
Methods	RCT Parallel assignment Triple blinded Duration: 15 days Multicenter: 6 centers (Créteil, Marseille, Nantes, Toulouse, Clermont‐Ferrand and Nice)
Participants	Estimated enrolment: 86 participants aged 7 years or older Inclusion criteria Aged 7 years or older and followed in the participating centres; age restriction due to children aged 7 years or more because as they have a better adherence to nebulization treatment than younger children Diagnosis of CF confirmed by sweat test (> 60 mmol/L) or the identification of 2 CF‐causing mutations (or both) Confirmed CRS by an otolaryngologist‐head and neck surgeon by endoscopic examination: bilateral mucopurulent secretions at middle meatus present longer than 12 weeks with or without nasal polyps Positive bacteria susceptibility to tobramycin in samples from middle meatus; susceptibility of bacteria to tobramycin confirmed Pulmonary examination before enrolment Exclusion criteria Oral antibiotic therapy 1 month before enrolment Enrolment in another protocol using antibiotic treatments Ongoing aerosolized tobramycin for endobronchial infection to avoid an overlap between treatment for lung and treatment for sinusitis Abnormal auditory acuity (increase of 20 dB hearing loss in auditory acuity) Hypersensitivity or allergy to aminoglycoside antibiotics FEV less than 25% or FVC of 40% or more of the value predicted for height Transplant recipient or currently on a transplant list Using nasal oxygen or under non‐invasive ventilation methods Women who are pregnant or breastfeeding
Interventions	Treatment arm 1 ampoule tobramycin (5 mL containing 300 mg of tobramycin and 11.25 mg of sodium chloride) nebulized nasally 2x per day (morning and evening with a maximum of 12 hours but not less than 6 hours between the 2 doses) each sonic nebulization lasting approximately 15 minutes; dosage will not be adjusted to body weight. Active intervention is manufactured by the "Pharmacie à Usage Interne" of the Henri Mondor Hospital prepared with Base Tobramycin and excipients in accordance with TOBI's composition Control arm 1 ampoule placebo (5 mL containing sodium chloride 0.9%) nebulized nasally 2x per day (morning and evening with a maximum of 12 hours but not less than 6 hours between the 2 doses) each sonic nebulization lasting approximately 15 minutes; dosage will not be adjusted to body weight. Placebo is manufactured by the "Pharmacie à Usage Interne" of the Henri Mondor Hospital so that it has the same colour (light yellow transparent) as tobramycin
Outcomes	Primary outcome Density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 15 Secondary outcomes Density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 30 and 90 Minimum inhibitor concentration of sputum bacteria to antibiotics at day 15, 30 and 90 Minimum inhibitor concentration of sputum bacteria to tobramycin at day 90 FVC in both groups at day 0 and day 30 FEV in 1 second in both groups at day 0 and day 30 Nasal obstruction at day 90 compared to baseline at day 0, 15, 30 and 90 Rhinorrhea compared to baseline at day 0, 15, 30 and 90 Mucopurulent secretions compared to baseline at day 0, 15, 30 and 90 Facial pain compared to baseline at day 0, 15, 30 and 90 Dysosmia compared to baseline at day 0, 15, 30 and 90 Nasal endoscopic scores compared to baseline in both groups at day 0, 15, 30 and 90 Score of the SM5 quality of life questionnaire in both groups at day 0, 15, 30 and 90 Score of the SNOT‐20 quality of life questionnaire in both groups at day 0, 15, 30 and 90 Hearing perceptual thresholds of the intensity (in dB hearing loss) and frequency (Hz) of sound waves at day 0 and day 30
Starting date	February 2017
Contact information	Virginie ESCABASSE, MD Tel: 1 45 17 55 97 ext 33 virginie.escabasse@chicreteil.fr
Notes

CF: cystic fibrosis
CFU: colony forming units
CRS: chronic rhinosinusitis
CT: computer tomography
FEV: forced expiratory volume
FVC: forced vital capacity
RCT: randomized controlled trial
SNOT: sino‐nasal outcomes test