Evaluation of the Efficacy of 3-month Continuous Extended Treatment With Azithromycin in Idiopathic Purulent Oedematous Sinusitis in Adults: a Multicentre Randomised Controlled Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Intercommunal Creteil

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

6 Oct 2022 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517239-33-00

EudraCT number

2020-001227-13

ClinicalTrials.gov

NCT05157685

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The evolution (intra-individual difference) of the specific quality of life score (Sino-Nasal Outcome Test 22 : SNOT 22) between inclusion and the end of 3 months of treatment.

Secondary objectives 4

1. Compare the efficacy of azithromycin DDLC to placebo at 3 months on o The number of infectious rhinosinus exacerbations o The number of courses of antibiotics administered o Intensity of functional symptomatology o Endoscopic examination results o CT score of rhinosinus opacities before treatment and after 3 months of treatment o Ciliary beat before treatment and after 3 months of treatment o The degree of nasal inflammation o Bacterial colonization o General quality of life o Absenteeism from work
2. To evaluate the compliance and tolerance of the treatment (clinical and biological tolerance)
3. Evaluate the remanence of the treatment at 6 months on the quality of life, the symptomatology, the nasal endoscopy and the bacteriological sampling.
4. To evaluate the clinico-biological predictive factors of response to treatment.

Conditions and MedDRA coding

Ear, nose and throat diseases

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient older than 18 years and less than 70 years of age
2. 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
3. Rebellious form of persistent purulent rhinosinusitis despite at least 2 antibiotic therapies prescribed according to HAS recommendations in force for ethmoid sinusitis
4. Signed informed consent of the patient
5. Membership in a health insurance plan or beneficiary

Exclusion criteria 25

1. Pregnancy or breastfeeding
2. PCOS of identified primary cause (identified immune deficiency, cystic fibrosis)
3. Chronic non-purulent rhinosinusitis (nasosinusal polyposis, allergic rhinosinusitis)
4. Localized chronic suppurative rhinosinusitis (single sinus, unilateral, frontal or maxillary or sphenoidal)
5. Severe hepatic insufficiency (factor V level < 50%)
6. Severe renal insufficiency (stage 4 (GFR < 30 ml/min/1.73 m2) and/or creatinine < 40 ml/min)
7. 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%)
8. Documented moderate pre-existing hearing loss (>30dB) or single ear (unilateral cophosis)
9. Major cognitive impairment or lack of French language skills preventing completion of SNOT-22 and SF-36 questionnaires
10. Patient with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases)
11. Patient with peanut or soy allergy
12. Patient allergic to macrolides
13. Patients who are intolerant or allergic to any of the excipients of azithromycin or placebo
14. Treatment with azithromycin in the previous 3 months
15. Long QT on ECG ((>440ms for male and >450ms for female) or cardiac arrhythmia or bradycardia (<60btm)
16. Hypokalemia or hypomagnesemia on blood ionogram
17. Confirmed or suspected atypical mycobacteriosis
18. Contraindicated drug combinations with macrolides (K-vitamins or drugs containing cisapride, colchicine, ergotamine or dihydroergotamine
19. 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 drug
20. Patients with severe cholestasi
21. Patients under guardianship or curatorsh
22. Patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation
23. History of facial radiotherapy
24. History of rhinosinus cancer
25. Participation in other category 1 research at the time of inclusion or in the month prior to inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Comparison of sinonasal outcome test (SNOT) 22 specific quality of life score averages

Secondary endpoints 21

1. Number of infectious rhinosinus exacerbations
2. Number of courses of antibiotics use
3. Visual analog scales of symptoms
4. Semi-quantitative symptom scale
5. Semi-quantitative nasal endoscopy score
6. Quantitative Lund MacKay CT score
7. Nasal inflammation flow
8. General quality of life Short form-36 (SF-36)
9. Days off work
10. Olfactory score
11. Bacteria present on the protected nasal swab
12. Number of participants with clinical adverse events as assessed by compliance
13. Number of participants with biological adverse events as assessed by compliance
14. Residual effect of the treatment using the SNOT 22 quality of life questionnaire
15. Residual effect of the treatment using the SF-36 quality of life questionnaires
16. Residual effect of the treatment using the VAS score
17. Residual effect of the treatment using the semi-quantitative symptom scale
18. Residual effect of the treatment using the nasal endoscopy
19. Residual effect of the treatment using the bacteriological samples.
20. Quantitative aspect of the ciliary beat
21. Qualitative aspect of the ciliary beat

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Intercommunal Creteil

Sponsor organisation

Centre Hospitalier Intercommunal Creteil

Address

40 Avenue De Verdun

City

Creteil

Postcode

94000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

BEQUIGNON Emilie

Public contact point

Organisation

Centre Hospitalier Intercommunal Creteil

Contact name

BEQUIGNON Emilie

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications