NAC Inhalation in the Treatment Of Symptomatic acuTe rhinosinUSitis (NOTUS)

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Rhinosinusitis; Acute Rhinosinusitis; Recurrent Acute Rhinosinusitis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 294

Contacts and Locations

• Study Contact: Name: Myung-Sook Hong; Phone Number: 82-2-708-8238; Email: mshong@boryung.co.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Yeouido St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with symptomatic acute rhinosinusitis (including recurrent acute rhinosinusitis and symptomatic acute-on-chronic rhinosinusitis).

Approximately 300 subjects (Re-enrollment is not allowed.)

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control sites; Group of patients receiving standard treatment for symptomatic acute rhinosinusitis
Test sites; Group of patients receiving NAC inhalation in addition to standard treatment for symptomatic acute rhinosinusitis

What is the study measuring?

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] The total score is sum of the investigator's symptomatic assessment scores (on nasal congestion, nasal/postnasal discharge, facial pain/sense of facial pressure, and reduction/loss of smell); the maximum total score is 12 and minimum total score is 0	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse drug reaction (ADR) incidence	Incidence and characteristics of NAC inhalation related adverse drug reactions	Day 0, Day 7, Day 14

Collaborators and Investigators

• Sponsor: Boryung Pharmaceutical Co., Ltd
• Investigators: Study Director: Myung-Sook Hong, Boryung Pharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): September 17, 2021
• Study Completion (Actual): September 17, 2021

Study Registration Dates

• First Submitted: October 16, 2019
• First Submitted That Met QC Criteria: October 16, 2019
• First Posted (Actual): October 18, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: N-acetylcysteine; rhinosinusitis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis
• Other Study ID Numbers: BR-NAC-OS-401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No