Effect of Post Operative Low Dose Oral Azithromycin in Chronic Rhinosinusitis Patients With Nasal Polyps

Chronic Rhinosinusitis with Nasal Polyps (CRSWNP) is a complex and persistent inflammatory disease of the paranasal sinus mucosa. It is clinically characterized by long-standing sinonasal mucosal inflammation, severe nasal congestion, continuous anterior and posterior rhinorrhea, facial pressure or fullness, and partial or complete loss of olfactory function. Functional Endoscopic Sinus Surgery (FESS) remains the primary surgical procedure of choice for CRSWNP cases that are refractory to conventional medical management. The ultimate goal of FESS is to restore surgical drainage pathways, improve sinus clearance, and re-establish proper sinus ventilation. This surgical intervention creates an anatomical environment optimal for post-operative topical medical therapies. Nevertheless, persistent mucosal inflammation, recalcitrant tissue edema, and post-operative recurrence of polypoid tissue represent major challenges during long-term follow-up. Despite initial surgical success, recurrent nasal polyposis remains a significant clinical challenge following Functional Endoscopic Sinus Surgery (FESS). In cases of recurrence, medical management plays a pivotal role in controlling mucosal inflammation and delaying or preventing re-operation. Diverse pharmacological interventions have been explored to control post-operative recurrence, including standard anti-inflammatory regimens as well as alternative systemic therapies such as some antibiotics, long-term macrolides, and novel biologics targeting specific inflammatory pathways. Macrolides, particularly 15-membered azalides such as Azithromycin, possess significant immunomodulatory and anti-inflammatory properties distinct from their classic antibacterial actions. When administered in low doses over extended periods, Azithromycin actively downregulates pro-inflammatory cytokines, inhibits tissue neutrophil infiltration, decreases goblet cell hypersecretion, and fosters mucosal healing and epithelial restoration.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)
• Intervention / Treatment: Drug: Azithromycin; Procedure: routine nasal douching

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Adult patients of both sexes aged ≥ 18 years.

  • Documented clinical and radiological diagnosis of Chronic Rhinosinusitis with Nasal Polyps (CRSWNP).
  • Patients with high baseline disease severity scores based on:
• CT Paranasal Sinuses Staging: High Lund-Mackay CT Score.
• Symptom Burden Assessment: High SNOT-22 Questionnaire Score. • Patients who comply with scheduled follow-up visits and appointments.

Exclusion Criteria:

• • Patients aged under 18 years (< 18 years).

  • Presence of unilateral nasal polyps, antrochoanal polyps, granuloma / granulomatous lesions, fungal
  • rhinosinusitis, or suspected benign or malignant sinonasal neoplasms.
  • Development of significant drug-related adverse effects, adverse reactions, or clinical complications during the
  • treatment course.
  • Known hypersensitivity or previous severe allergic reactions to macrolide antibiotics.
  • Baseline prolonged QTc interval, active cardiac arrhythmias, or significant cardiovascular disease.
  • Pre-existing significant impairment of hepatic or renal functions.
  • Pregnant and lactating female patients.
  • Patients who fail to adhere to follow-up visits or refuse to sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study Group; Patients will receive post-operative oral Azithromycin at a dose of 500 mg three times weekly in combination with routine nasal douching (alkaline/saline nasal irrigation three times daily) for a total duration of 12 weeks.	Drug: Azithromycin; oral Azithromycin at a dose of 500 mg three times weekly; Procedure: routine nasal douching; alkaline/saline nasal irrigation three times daily) for a total duration of 12 weeks.
Placebo Comparator: Control Group; Patients will be treated with routine nasal douching alone (alkaline/saline nasal irrigation three times daily) for a total duration of 12 weeks.	Procedure: routine nasal douching; alkaline/saline nasal irrigation three times daily) for a total duration of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
recurrence rate of rhinosinusitis after low-dose oral azithromycin	12 week

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 19, 2026
• First Submitted That Met QC Criteria: August 19, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 19, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Macrolides; Lactones; Erythromycin; Polyketides; Azithromycin
• Other Study ID Numbers: azithromycin in rhinosinusitis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes