Evaluating Azithromycin for Chronic Sinusitis

Inclusion Criteria:

* Patient older than 18 years and less than 70 years of age
* Chronic rhinosinusitis (\> 12 weeks of evolution) meeting the definition published in the European Paper Position2012 (1) and corresponding exclusively to the following endoscopic and CT criteria:

  * Nasal endoscopy showing bilateral and diffuse involvement associating edema of the mucosa of the nasal cavities and meatus with the presence of mucopurulent secretions in these areas
  * Nasosinus CT scan showing diffuse and bilateral pansinus opacities involving at least the maxillary sinuses and the anterior and posterior ethmoids
* Persistent intractable purulent rhinosinusitis despite at least 2 antibiotic therapies
* 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 or maxillary or sphenoidal)
* Severe hepatic insufficiency (factor V level \< 50%)
* Severe renal insufficiency (stage 4 (GFR \< 30 ml/min/1.73 m2) and/or creatinine \< 40 ml/min)
* Severe heart failure (old age, ischemic heart disease, episode of recurrent cardiac arrest; hypotension, NYHA functional stage III-IV; widened QRS, complex ventricular arrhythmias; hyponatremia (Na \<135mmol/l); stage 4 renal failure (GFR \< 30 ml/min/1.73 m2); severely depressed LVEF (\< 30%)
* Documented moderate pre-existing sensorineural hearing loss with a mean pure tone threshold 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 completion of SNOT-22 and SF-36 questionnaires
* Patient with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption 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 or placebo
* Treatment with azithromycin in the previous 3 months
* Long QT on ECG ((\>440ms for male and \>450ms for female) or cardiac arrhythmia or bradycardia (\<60btm).The calculation of the corrected QT should be carried out using the Bazett formula.
* Hypokalemia or hypomagnesemia on blood ionogram
* Confirmed or suspected atypical mycobacteriosis
* Contraindicated drug combinations with macrolides (K-vitamins or drugs containing cisapride, colchicine, ergotamine or dihydroergotamine)
* Cautionary drug combinations (non-inclusion criteria)

  * Atorvastatin (Increased risk of concentration-dependent rhabdomyolysis-type adverse events due to decreased hepatic metabolism of the cholesterol-lowering drug.
  * Ciclosporin (risk of increased ciclosporin blood levels and creatinine levels)
  * Digoxin (increase in digoxemia due to increased absorption of digoxin), Drugs likely 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), certain fluoroquinolones (e.g. moxifloxacin, levofloxacin) (increased risk of ventricular rhythm disturbances)
  * Simvastatin (increased risk of rhabdomyolysis-type adverse effects (concentration-dependent), due to decreased hepatic metabolism of the cholesterol-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 cell transplantation
* History of facial radiotherapy
* History of rhinosinus cancer
* Participation in other category 1 research at the time of inclusion or in the month prior to inclusion