Evaluation of the Efficacy of Azithromycin in Idiopathic Purulent Oedematous Sinusitis in Adults

Inclusion Criteria:

• Patient older than 18 years and less than 70 years of age

• Chronic rhinosinusitis (> 12 weeks of evolution) meeting the definition published inthe European Paper Position2012 (1) and corresponding exclusively to the followingendoscopic and CT criteria:

• Nasal endoscopy showing bilateral and diffuse involvement associating edema ofthe mucosa of the nasal cavities and meatus with the presence of mucopurulentsecretions in these areas

• Nasosinus CT scan showing diffuse and bilateral pansinus opacities involving atleast the maxillary sinuses and the anterior and posterior ethmoids

• Persistent intractable purulent rhinosinusitis despite at least 2 antibiotictherapies

• Signed informed consent of the patient

• Membership in a health insurance plan or beneficiary

Exclusion Criteria:

• Pregnancy or breastfeeding

• PCOS of identified primary cause (identified immune deficiency, cystic fibrosis,HIV)

• Chronic non-purulent rhinosinusitis (nasosinusal polyposis, allergic rhinosinusitis)

• Localized chronic suppurative rhinosinusitis (single sinus, unilateral, frontal ormaxillary or sphenoidal)

• Severe hepatic insufficiency (factor V level < 50%)

• Severe renal insufficiency (stage 4 (GFR < 30 ml/min/1.73 m2) and/or creatinine < 40ml/min)

• Severe heart failure (old age, ischemic heart disease, episode of recurrent cardiacarrest; hypotension, NYHA functional stage III-IV; widened QRS, complex ventriculararrhythmias; hyponatremia (Na <135mmol/l); stage 4 renal failure (GFR < 30ml/min/1.73 m2); severely depressed LVEF (< 30%)

• Documented moderate pre-existing sensorineural hearing loss with a mean pure tonethreshold in the poorer ear in bone conduction >30 dB across all 3 frequencies (500, 1000 and 2000 Hz) or in only one ear (unilateral deafness).

• Major cognitive impairment or lack of French language skills preventing completionof SNOT-22 and SF-36 questionnaires

• Patient with galactose intolerance, total lactase deficiency or glucose-galactosemalabsorption syndrome (rare hereditary diseases)

• Patient with peanut or soy allergy

• Patient allergic to macrolides

• Patients who are intolerant or allergic to any of the excipients of azithromycin orplacebo

• Treatment with azithromycin in the previous 3 months

• Long QT on ECG ((>440ms for male and >450ms for female) or cardiac arrhythmia orbradycardia (<60btm).The calculation of the corrected QT should be carried out usingthe Bazett formula.

• Hypokalemia or hypomagnesemia on blood ionogram

• Confirmed or suspected atypical mycobacteriosis

• Contraindicated drug combinations with macrolides (K-vitamins or drugs containingcisapride, colchicine, ergotamine or dihydroergotamine)

• Cautionary drug combinations (non-inclusion criteria)

• Atorvastatin (Increased risk of concentration-dependent rhabdomyolysis-typeadverse events due to decreased hepatic metabolism of the cholesterol-loweringdrug.

• Ciclosporin (risk of increased ciclosporin blood levels and creatinine levels)

• Digoxin (increase in digoxemia due to increased absorption of digoxin), Drugslikely to cause torsades de pointes, in particular class IA (e.g. quinidine)and class III (e.g. amiodarone, sotalol) antiarrhythmics, antipsychotics (e.g.phenothiazines, pimozide), tricyclic antidepressants (e.g. citalopram), certainfluoroquinolones (e.g. moxifloxacin, levofloxacin) (increased risk ofventricular rhythm disturbances)

• Simvastatin (increased risk of rhabdomyolysis-type adverse effects (concentration-dependent), due to decreased hepatic metabolism of thecholesterol-lowering agent)

• Ivabradine (increased risk of ventricular rhythm disorders),

• Hypokalemic drugs

• Bradycardia drugs

• Patients with severe cholestasis

• Patients under guardianship or curatorship

• Patients with hematologic malignancies who have undergone hematopoietic stem celltransplantation

• History of facial radiotherapy

• History of rhinosinus cancer

• Participation in other category 1 research at the time of inclusion or in the monthprior to inclusion