NAC Inhalation in the Treatment Of Symptomatic acuTe rhinosinUSitis

Study Overview
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Brief Summary
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N-acetylcysteine (NAC), known to have mucolytic and antioxidant effects, is widely used to treat respiratory diseases and manage post-surgery pulmonary complications. It is also administered as a treatment for acetaminophen addiction and a preventive measure for contrast-induced nephropathy (CIN). While NAC inhalation is commonly used for mucolytic purpose for various respiratory disease because it has relatively less side effects compared to oral or injection administrations, it is more used as a part of allopathy than as a major therapy. As a result, there is neither enough relevant clinical data nor specific reference in treatment guidelines. Therefore, this study aims to evaluate the overall treatment effectiveness and safety of NAC inhalation compared with standard treatment, and to perform follow-up observations on administration cases, patient characteristics, and adverse events of NAC inhalation used in real clinical settings.

Detailed Description
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Study Methodology : 12 medical institutions in Korea that meet the inclusion criteria are cluster-randomized (test sites : control sites =1:1). Information about randomization is disclosed to both investigators and subjects. This means both study center investigators and subjects will be aware of the purpose of this study as well as the result of randomization (whether the subjects will receive NAC inhalation or not) from the beginning of the study. Investigators shall obtain voluntary consent for participation in this research from patients who visit their medical institutions with symptomatic acute rhinosinusitis within the study duration. Patients who provided a written consent for the use of their personal information and who satisfy inclusion/exclusion criteria will be given a study enrollment number and available data on these patients will be collected among the predefined study relevant data in the case reports until Day 14 (±3 days) from the starting day of treatment. Statistical Analysis Methods (Analysis of primary endpoints) : Obtain descriptive statistics (average, standard deviation, median, minimum, quartile, and maximum) for the change in the total score of the investigator's symptomatic severity assessment by treatment group on Day 14 compared with each time point and baseline (Day 0). Paired t-test shall be used to check intra-group change difference and Two sample t-test shall be used to check inter-group change difference.

Official Title
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A Cluster-randomized, Open, Prospective, Observational Study to Evaluate the Treatment Effectiveness and Safety of N-acetylcysteine(NAC) Inhalation Compared With Standard Treatment in Patients With Symptomatic Acute Rhinosinusitis

Conditions
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Acute Rhinosinusitis, Recurrent Acute Rhinosinusitis, Chronic Rhinosinusitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are explained about the study objectives and methodologies, and shall express their consent by signing a written agreement for the use of their personal information. Male and female patients who are ≥ 18 years old. Symptomatic acute rhinosinusitis patients whose symptoms have been present for more than 1 week and less than 12 weeks; recurrent acute rhinosinusitis patients (acute rhinosinusitis relapsed 3 times or more within 6 months, sub-clinical symptoms between the relapses); or, symptomatic acute-on-chronic (12 weeks or more) rhinosinusitis patients. [Patients display 2 or more symptoms that imply rhinosinusitis infection. The displayed symptoms should include at least one or more cardinal symptoms (nasal congestion or nasal/postnasal discharge).] The total score of the investigator's symptomatic severity assessment for a patient is 4 or above, and four symptomatic aspects (nasal congestion, nasal/postnasal discharge, facial pain/sense of facial pressure, reduction/loss of smell) are rated in four categories (0=no symptom, 1=mild, 2=moderate, 3=severe). Patients have anterior rhinoscopy or nasal endoscopy results, and one or more of the following are observed: Redness, Edema or mucosal obstruction(mostly in the middle nasal), Mucopurulent discharge(mostly in the middle nasal), Nasal polyps Exclusion Criteria: Patients with rhinosinusitis of dental origin. Patients with a known chronic pulmonary symptoms including bronchial asthma and chronic bronchitis. Patients with nasal obstruction to the extent that drug administration is difficult. Patients who have received endoscopic sinus surgery within the last 3 months. Patients who have shown hypersensitivity or are likely to show hypersensitivity to N-acetylcysteine inhalation components (for the test sites) Pregnant or breast-feeding patients. Patients who are currently participating in other clinical trials (clinical trials for drugs or medical devices) or are planning to participate in other clinical trials during the duration of this study. Patients who are not suitable for study participation upon the investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control sites<br>Group of patients receiving standard treatment for symptomatic acute rhinosinusitis | |
| Test sites<br>Group of patients receiving NAC inhalation in addition to standard treatment for symptomatic acute rhinosinusitis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the total score of the investigator's symptomatic severity assessment (Day 0, Day 14) | Assessed symptoms: nasal congestion, nasal/postnasal discharge, facial pain/sense of facial pressure, reduction/loss of smell are rated in four categories [0=no symptom, 1=mild, 2=moderate, 3=severe] | Day 0(enrollment) and Day 14 after treatment for rhinosinusitis | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total score of the investigator's symptomatic severity assessment | Change in the total score of the investigator's symptomatic severity assessment by treatment group on Day 7 compared with each time point and baseline (Day 0). Assessed symptoms: nasal congestion, nasal/postnasal discharge, facial pain/sense of facial pressure, reduction/loss of smell are rated in four categories [0=no symptom, 1=mild, 2=moderate, 3=severe] | Day 0, Day 7 | 
| Change in the score of the investigator's symptomatic severity assessment | Change in the score of the investigator's symptomatic severity assessment by treatment group on Day 7 and Day 14 compared with each time point and baseline (Day 0). Assessed symptoms: nasal congestion, nasal/postnasal discharge, facial pain/sense of facial pressure, reduction/loss of smell are rated in four categories [0=no symptom, 1=mild, 2=moderate, 3=severe] | Day 0, Day 7, Day 14 | 
| Change in the investigator's symptomatic existence assessment | The investigator's symptomatic severity assessment score shall be categorized into 'With Symptom/Without Symptom' to calculate frequency and rate of the investigator's symptomatic existence assessment for each group at each time point. Without Symptom: If the investigator's symptomatic severity score is '0=no symptom.' With Symptom: If the investigator's symptomatic severity score includes one of '1=mild,' '2=moderate,' or '3=severe.' | Day 0, Day 7, Day 14 | 
| Change in the subjects' 100 mm VAS scores for overall symptomatic severity | Change in the subjects' 100 mm VAS scores for overall symptomatic severity by treatment group on Day 7 and Day 14 compared with each time point and baseline (Day 0). [0mm=No symptom   100mm=Severe symptom] | Day 0, Day 7, Day 14 | 
| Change in SNOT-20 scores | Individual and total SNOT-20 scores by group on Day 14 compared with each time point and baseline (Day 0). [0=No problem, 1=Very mild problem, 2=Mild or Slight problem, 3=Moderate problem, 4=Severe problem, 5=Problem as bad as can be / maximum score=100] | Day 0, Day 14 | 
| The rate of residual symptomatic subjects on Day 14 (based on the investigator's symptomatic assessment) | Calculate frequency and rate of the residual symptomatic subjects by group on Day 14. | Day 14 | 
| Rhinosinusitis complication incidence | Calculate frequency and rate of the subjects who experienced rhinosinusitis complications(preseptal cellulitis, orbital cellulitis, intracranial abscess, meningitis, osteomyelitis, etc.) by group during the study period. | Day 14 | 
| Correlation between 100mm VAS and the investigator's symptomatic severity assessment | Calculate Pearson's correlation coefficient for the subjects' 100 mm VAS and the total score of the investigator's symptomatic severity assessment by group for each time point. | Day 0, Day 7, Day 14 | 
| Correlation between SNOT-20 and the investigator's symptomatic severity assessment | Calculate Pearson's correlation coefficient for the total SNOT-20 scores and the total score of the investigator's symptomatic severity assessment. | Day 0, Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhinosinusitis, N-acetylcysteine