A Phase 3 interventional study of Azithromycin Oral Tablet and Placebo in Sinusitis, Chronic and Sinus Infection Chronic, sponsored by Centre Hospitalier Intercommunal Creteil. Recruiting at 13 sites in France. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-08-29.
Sponsored by Centre Hospitalier Intercommunal Creteil · Phase 3, Interventional, and Treatment
Purulent Oedematous Sinusitis (POS) is a particular form of chronic rhinosinusitis observed in 2% of the general population. In spite of its heavy impact on the quality of life, There is no established recommendation for the treatment of primary POS. Long-term low-dose macrolides are currently proposed for these forms of chronic rhinosinusitis when conventional treatments (local corticosteroids, saline rinsing, iterative short courses of antibiotics targeted on pathogens, and surgical opening and drainage) have failed. This treatment with macrolides is currently applied off-label.
This study aims to assess the efficacy of macrolides in POS. An extensive workup is fulfilled to exclude other forms of chronic rhinosinusitis (Th2 biased inflammatory diseases, allergic diseases) (allergy, nasosinusal polyposis) or those due to cystic fibrosis or immune deficiency.
POS is a particular form of chronic rhinosinusitis described in 2% of the general population. They lead to an alteration in the quality of daily life with a significant impact on the professional life of 70% of patients. They can be of idiopathic or of secondary origin. The most frequent secondary forms are those observed in cystic fibrosis and immune deficiencies. The pathophysiology of primary POS remains poorly understood, involving Th1-type inflammation and various bacteria (with Staphylococcus Aureus in the forefront). Bacteria could impair the ciliary beat, perpetuating infection and mucosal inflammation. There is no established recommendation for the treatment of primary POS Long-term low-dose macrolides are currently proposed for these forms of chronic rhinosinusitis when conventional treatments (local corticosteroids, saline rinsing, iterative short courses of antibiotics adapted to the germs found, and surgical drainage) have failed. This treatment with macrolides is currently used off label.
Macrolides are effective on most gram-positive and gram-positive bacteria. Macrolides also have immunomodulatory properties on the Th1 immune response. This effect is maintained even in the presence of macrolide-resistant bacteria. In chronic obstructive pulmonary disease, daily administration of half-dose macrolides over the long term (HDLT) has been shown to be effective in reducing the frequency of infectious exacerbations. Uncontrolled trials have described an improvement in symptom scores in chronic rhinosinusitis with or without polyps. The results observed in randomized trials versus placebo are contradictory. A meta-analysis published in 2013 based on these 2 randomized studies was inconclusive regarding the efficacy of HDLT macrolides. The heterogeneity of the inclusion criteria with rhinosinusitis of a different proTh-2 inflammatory profile corresponding to that usually observed in nasal polyposis could explain this lack of result. A review of the literature published in 2017 on HDLT macrolides based on 52 publications observed a very wide diversity of antibiotic protocols in terms of the molecule chosen, the administration scheme and the duration of treatment (8 to 24 weeks). The number of patients studied was often small, which affected the statistical power of the results obtained. The authors of this review conclude by stressing the need to conduct placebo-controlled studies on large populations of patients selected on the phenotypic level.
This study propose to evaluate the value of HDLT macrolides in this specific etiological setting. This project plans to exclude all chronic rhinosinusitis of Th2 inflammatory origin (allergy, nasosinusal polyposis) or those due to cystic fibrosis or immune deficiency. In addition, the inclusion centers selected in Ile de France have the necessary expertise to evaluate the impact of azithromycin on mucociliary clearance, notably with the development of innovative tools to measure the efficiency of the ciliary beat (high-speed video microscopy and particle tracking).At the same time, the tolerance of HDLT macrolides measured in patients with cystic fibrosis or chronic obstructive pulmonary disease (COPD) is excellent, provided that the well-documented contraindications are respected. No serious adverse effects have been reported, apart from cases of transient or permanent moderate hearing loss requiring audiometric monitoring.
No specific study regarding the treatment of primary POS is available to date, even tough POS is very prevalent and its management is still associated with poor patient-reported outcomes.
256 studies on the registry are indexed under Sinusitis; 23 are open to participants now.
This study's planned enrollment of 230 is above the median of 60 across 196 interventional studies indexed under Sinusitis.
Browse Sinusitis studies →Centre Hospitalier Intercommunal Creteil is the lead sponsor of 131 studies on the registry; 36 are open to participants now.
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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:
Exclusion Criteria:
Cautionary drug combinations (non-inclusion criteria)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Azithromycin 250 mg once daily morning or evening (with or without meals)
Drug: Azithromycin Oral Tablet
Placebo once daily morning or evening (with or without meals)
Drug: Placebo
Treatment assigned by randomization will be prescribed immediately. The active or placebo will be dispensed by the centre's pharmacy. Treatment will be taken in the morning or evening for 3 months.
Also known as: active arm
Treatment assigned by randomization will be prescribed immediately. The active or placebo will be dispensed by the centre's pharmacy. Treatment will be taken in the morning or evening for 3 months.
Also known as: comparator arm
Comparison of sinonasal outcome test (SNOT) 22
Comparison of the means of the Sinonasal Outcome Test (SNOT 22) specific quality of life scores after 3 months of treatment. (min = 0, max = 110)
Time frame: 3 months
Number of infectious rhinosinus exacerbations
The number of infectious rhinosinus exacerbations during the 3-month period,
Time frame: 3 months
Number of courses of antibiotics used
Number of courses of antibiotics used during the 3-month period other than azithromycin or placebo
Time frame: 3 months
Visual analog scales of symptoms
Visual analog scales (VAS) of symptoms (self-assessment) (nasal obstruction, rhinorrhea, facial pain, smell disorder, nasal hyperactivity, epistaxis). The VAS measures the intensity of pain on a scale from 0 to 10.
Time frame: 6 months
Semi-quantitative symptom scale
Semi-quantitative 4-point symptom scale assessed by the practitioner (min = 0, max = 3)
Time frame: 6 months
Semi-quantitative nasal endoscopy score
Semi-quantitative nasal endoscopy score (0: absent/1: present) for each of the following items: presence of pus, edema, erythema, crusts, polyps, scored out of 5 per nasal cavity (maximum score of 10) (Lund Kennedy score),
Time frame: 6 months
Quantitative Lund MacKay CT score
Quantitative Lund MacKay CT score (0: no sinus opacity, 1: moderate opacity, 2: total opacity) measured on 12 for each side (score of 24 maximum),
Time frame: 6 months
Nasal inflammation flow
Nasal inflammation (nasal nitric oxide (NO) flow, neutrophil polynuclear cell (NPC) and lymphocyte infiltrate on nasal cytology and assays of interleukin 6, 8 and elastase produced by NPCs in nasal secretions)
Time frame: 6 months
General quality of life
General quality of life Short form 36 (SF-36) (min=1, max=100)
Time frame: 6 months
Days off work
Number of days off work in the 3 months prior to treatment and the number of days off work during the 3 months of treatment
Time frame: 6 months
Olfactory score
Olfactory score (sniffing's stick test),
Time frame: 6 months
Bacteria present on the protected nasal swab
Identification and quantification of bacteria observed on the protected nasal swab (semi-quantitative score
Time frame: 6 months
Number of participants with clinical adverse events as assessed by compliance
Clinical tolerance evaluated by the effective intake of tablets
Time frame: 3 months
Number of participants with biological adverse events as assessed by compliance
Biological tolerance evaluated by the effective intake of tablets
Time frame: 3 months
Residual effect of the treatment using the SNOT 22 quality of life questionnaires
At 6 months (i.e., 3 months after cessation of treatment), the residual effect of treatment will be measured using the SNOT 22 quality of life questionnaires
Time frame: 6 months
Residual effect of the treatment using the SF-36 quality of life questionnaires
At 6 months (i.e., 3 months after cessation of treatment), the residual effect of treatment will be measured using the SF-36 quality of life questionnaires
Time frame: 6 months
Residual effect of the treatment using the VAS score
At 6 months (i.e., 3 months after cessation of treatment), the residual effect of treatment will be measured using the VAS score. The VAS measures the intensity of pain on a scale from 0 to 10.
Time frame: 6 months
Residual effect of the treatment using the semi-quantitative symptom scale
At 6 months (i.e., 3 months after cessation of treatment), the residual effect of treatment will be measured using the semi-quantitative symptom scale
Time frame: 6 months
Residual effect of the treatment using the nasal endoscopy
At 6 months (i.e., 3 months after cessation of treatment), the residual effect of treatment will be measured using the nasal endoscopy
Time frame: 6 months
Residual effect of the treatment using the bacteriological samples.
At 6 months (i.e., 3 months after cessation of treatment), the residual effect of treatment will be measured using the bacteriological samples.
Time frame: 6 months
Quantitative aspect of the ciliary beat
Quantitative aspect of the ciliary beat (frequency of the beat in Hertz) on a small number of centers having the equipment
Time frame: 6 months
Qualitative aspect of the ciliary beat
Qualitative aspect of the ciliary beat (coordination (normal or dyskinetic), index of efficiency)) on a small number of centers having the equipment
Time frame: 6 months
Plan to share: No
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Studies of the drug tested here: Azithromycin
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