Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis

• Sponsor: Sandoz (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04123405
• Collaborator: (none)
• Enrollment: 944
• Locations: 37
• Arms: 4
• Actual Duration (Months): 5.9
• Patients Per Site: 25.5
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief Summary

The trial was conducted as a prospective, randomized, multinational, multicenter, double-blind study in 4 parallel groups of patients.

Condition or Disease	Intervention/Treatment	Phase
Rhinosinusitis	Drug: acetylcysteine; Drug: Placebo	Phase 3

Detailed Description

The study was the prospective, randomized, multinational, multicenter, double-blind study in 4 parallel groups of patients.

Patients underwent screening examinations at Visit 1. Patients who met all inclusion/ no exclusion criteria were randomized at the baseline visit (Day 1) to the double-blind treatment for a duration of 14 days but in case of delayed final visit (Day 15) the patient could voluntarily take reserve study medication for a maximum of 3 additional days.

After the end of the double-blind treatment phase, the patients underwent an end-of-treatment (EOT) examinations on Day 15 (+3).

A follow-up phone call within 7 days after Day 15 (or earlier in case of premature termination) was performed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 944 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis: a Prospective, Randomized, Double-blind, Placebo-controlled Trial
• Actual Study Start Date: Oct 22, 2020
• Actual Primary Completion Date: Apr 20, 2021
• Actual Study Completion Date: Apr 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A: 600 mg acetylcysteine one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	Drug: acetylcysteine; 600 mg tablet; Drug: Placebo; Placebo to acetylcysteine
Experimental: Group B: 1200 mg acetylcysteine two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	Drug: acetylcysteine; 600 mg tablet; Drug: Placebo; Placebo to acetylcysteine
Experimental: Group C: 2400 mg acetylcysteine four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	Drug: acetylcysteine; 600 mg tablet
Placebo Comparator: Group D: Placebo four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	Drug: Placebo; Placebo to acetylcysteine

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set [Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.

2. Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set [Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.

Secondary Outcome Measures

1. Time to Onset of Action, Full Analysis Set [Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value<0.05) improvement from placebo.

2. Time to Onset of Action, Per-Protocol Set [Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value<0.05) improvement from placebo.

3. Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set [Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.

4. Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set [Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15]

   The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.

5. Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set [Baseline (Day 1), Day 7 and Day 14]

   SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL.

6. Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set [Baseline (Day 1), Day 7 and Day 14]

   SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL.

7. Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set [Baseline (Day 1), Day 7 and Day 14]

   SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome.

8. Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set [Baseline (Day 1), Day 7 and Day 14]

   SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome.

9. Number of Responders and Non-responders to Treatment, Full Analysis Set [Day 4, 7, 10 and 15]

   Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.

10. Number of Responders and Non-responders to Treatment, Per-Protocol Set [Day 4, 7, 10 and 15]

    Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female subjects aged between 14 and 75 years inclusive on the date of consent

2. Diagnosis of acute, uncomplicated rhinosinusitis defined at screening visit 1 and at

Visit 2 as:

1. major symptom score (MSS) assessed by the patient ≥8 and ≤12 points for the following: rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure, whereupon the nasal congestion is mandatory and no more than 3 of the 5 symptoms are rated as severe

2. individual score for facial pain/pressure ≥1 (mild) and ≤2 (moderate)

3. presence of symptoms ≤3 days prior to screening visit

4. For adults (≥18 years): Informed consent to participate in the trial provided in written form; For adolescents (≥14 - <18 years): own subject informed consent/ assent to participate in the trial and the informed consent from all parent(s)/ legal guardian(s) provided in written form.

Exclusion Criteria:

1. History of hypersensitivity or intolerance to the active substance or any of the excipients of the trial medication

2. Patient with history of hereditary fructose intolerance, galactose intolerance, lactase deficiency or glucose-galactose malabsorption

3. Chronic rhinosinusitis (symptoms lasting longer than 3 months)

4. Subjects who have undergone sinus or nasal surgery for chronic rhinosinusitis in the 6 months prior to screening visit

5. Sinus lavage within 7 days prior to screening visit

6. Odontogenic rhinosinusitis

7. Allergic (perennial or seasonal) rhinitis

8. Bronchial asthma or chronic obstructive pulmonary disease

9. Nasal polyposis or clinically relevant nasal septum deviation

10. Concomitant otitis

11. Intranasal or systemic use of corticosteroids within 30 days prior to screening visit

12. Intranasal or systemic use of antibiotics within 30 days prior to screening visit

13. Use of nasal decongestants within 2 days prior to screening visit

14. Concomitant treatment of common cold-like symptoms within 7 days prior to screening visit with any of the following:

15. Analgesics

16. Non-steroidal anti-inflammatory drugs

17. Antihistamines

18. Concomitant use of intranasal saline irrigation

19. Use of immunosuppressive agents within 30 days prior to screening visit

20. Immunocompromised state

21. Suspicion for acute bacterial rhinosinusitis (defined as presence of purulence for 3 to 4 days with fever ≥ 38.3°C)

22. Pregnant or breast-feeding female patient

23. Female patient of childbearing potential (not surgically sterilized/hysterectomized or postmenopausal for at least 1 year) who is not currently using (documented at screening visit) and not willing to use medically reliable methods of contraception for the entire trial duration such as oral, injectable or implantable contraceptives, intrauterine contraceptive devices (IUD), sexual abstinence or vasectomized partner

24. Any other condition of the patient (e.g. serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the trial treatment or may jeopardize patient's safety, compliance or adherence to protocol requirements

25. Participation in ANY research study involving another investigational medicinal product (IMP) within 30 days prior to screening visit, or simultaneous participation in another clinical study or previous participation in present study

26. Suspected alcohol/ drug dependence or abuse (including heavy smoking: ≥ 20 cigarettes daily)

27. Use of snuff tobacco

28. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial

29. Subjects who are known or suspected:

• not to comply with the trial directives

• not to be reliable or trustworthy

• to be a dependent person, e.g. a relative, family member, or member/employee of the investigator's or sponsor's staff

• subject is in custody or submitted to an institution due to a judicial order.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sandoz Investigative Site	Burgas		Bulgaria	8000
2	Sandoz Investigative Site	Gabrovo		Bulgaria	5300
3	Sandoz Investigative Site	Plovdiv		Bulgaria	4000
4	Sandoz Investigative Site	Sliven		Bulgaria	8800
5	Sandoz Investigative Site	Sofia		Bulgaria	1000
6	Sandoz Investigative Site	Sofia		Bulgaria	1408
7	Sandoz Investigative Site	Sofia		Bulgaria	1527
8	Sandoz Investigative Site	Sofia		Bulgaria	1606
9	Sandoz Investigative Site	Yambol		Bulgaria	8600
10	Sandoz Investigative Site	Aachen		Germany	52074
11	Sandoz Investigative Site	Dresden		Germany	01139
12	Sandoz Investigative Site	Duisburg		Germany	47051
13	Sandoz Investigative Site	Chișinău		Moldova, Republic of	2012
14	Sandoz Investigative Site	Chișinău		Moldova, Republic of	2025
15	Sandoz Investigative Site	Chișinău		Moldova, Republic of	2032
16	Sandoz Investigative Site	Chișinău		Moldova, Republic of	2044
17	Sandoz Investigative Site	Chișinău		Moldova, Republic of	2051
18	Sandoz Investigative Site	Chișinău		Moldova, Republic of	37
19	Sandoz Investigative Site	Orhei		Moldova, Republic of	3005
20	Sandoz Investigative Site	Kazan		Russian Federation	420029
21	Sandoz Investigative Site	Kemerovo		Russian Federation	650066
22	Sandoz Investigative Site	Moscow		Russian Federation	117552
23	Sandoz Investigative Site	Moscow		Russian Federation	119571
24	Sandoz Investigative Site	Moscow		Russian Federation	123184
25	Sandoz Investigative Site	Moscow		Russian Federation	142190
26	Sandoz Investigative Site	Novosibirsk		Russian Federation	630051
27	Sandoz Investigative Site	Ryazan		Russian Federation	390026
28	Sandoz Investigative Site	Saint Petersburg		Russian Federation	191025
29	Sandoz Investigative Site	Saint Petersburg		Russian Federation	191186
30	Sandoz Investigative Site	Saint Petersburg		Russian Federation	192283
31	Sandoz Investigative Site	Saint Petersburg		Russian Federation	194291
32	Sandoz Investigative Site	Saint Petersburg		Russian Federation	195197
33	Sandoz Investigative Site	Saint Petersburg		Russian Federation	196084
34	Sandoz Investigative Site	Saint Petersburg		Russian Federation	196158
35	Sandoz Investigative Site	Smolensk		Russian Federation	214031
36	Sandoz Investigative Site	St. Petersburg		Russian Federation	197376
37	Sandoz Investigative Site	Yaroslavl		Russian Federation	150000

Sponsors and Collaborators

• Sandoz

Investigators

• Study Director: Sandoz, Sandoz

Study Documents (Full-Text)

• Study Protocol - Aug 14, 2020
• Statistical Analysis Plan - Oct 7, 2020

More Information

Publications

None provided.

• Responsible Party: Sandoz
• ClinicalTrials.gov Identifier: NCT04123405
• Other Study ID Numbers: 2018-08-EFT-1; 2019-000060-20
• First Posted: Oct 10, 2019
• Last Update Posted: Nov 19, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sandoz: acute uncomplicated rhinosinusitis, acetylcysteine
• Additional relevant MeSH terms: Sinusitis; Acetylcysteine; N-monoacetylcystine

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 42 clinical centers located in Bulgaria, Germany, Moldova and Russia.
Pre-assignment Detail	Participants were randomized in 1:1:1:1 ratio

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily).
Period Title: Overall Study
STARTED	235	238	238	233
Full Analysis Set	235	236	238	230
Per-protocol Set	213	215	212	207
Safety Set	235	238	238	233
COMPLETED	231	231	235	225
NOT COMPLETED	4	7	3	8

Baseline Characteristics

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo	Total
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily).	Total of all reporting groups
Overall Participants	235	238	238	233	944
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.0 (13.8)	40.7 (13.6)	41.3 (13.1)	41.1 (14.0)	41.0 (13.6)
Sex: Female, Male (Count of Participants)
Female	128 54.5%	142 59.7%	145 60.9%	141 60.5%	556 58.9%
Male	107 45.5%	96 40.3%	93 39.1%	92 39.5%	388 41.1%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	230 97.9%	235 98.7%	232 97.5%	231 99.1%	928 98.3%
Asian	4 1.7%	2 0.8%	5 2.1%	2 0.9%	13 1.4%
Unknown	1 0.4%	1 0.4%	1 0.4%	0 0%	3 0.3%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set
Description	The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time Frame	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	235	236	238	230
Mean (Standard Deviation) [Score on a scale]	-4.8213 (1.98247)	-4.7394 (1.99090)	-4.7758 (1.96938)	-5.0180 (1.98262)

2. Primary Outcome

Title	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set
Description	The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time Frame	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	213	215	212	207
Mean (Standard Deviation) [Score on a scale]	-4.9085 (1.92431)	-4.8688 (1.84448)	-4.8002 (1.90569)	-5.1256 (1.95072)

3. Secondary Outcome

Title	Time to Onset of Action, Full Analysis Set
Description	Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value<0.05) improvement from placebo.
Time Frame	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	235	236	238
Number [Days]	NA	NA	NA

4. Secondary Outcome

Title	Time to Onset of Action, Per-Protocol Set
Description	Time to onset of action was defined as first day of active treatment on which MSS showed statistically significant (p value<0.05) improvement from placebo.
Time Frame	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	213	215	212
Number [Days]	NA	NA	NA

5. Secondary Outcome

Title	Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set
Description	The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time Frame	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	235	236	238	230
Day 1 (Baseline)	9.634 (1.1181)	9.640 (1.0647)	9.702 (1.0101)	9.683 (1.0652)
Day 2	9.021 (2.0348)	9.004 (1.9883)	9.038 (2.1235)	9.074 (1.9866)
Day 3	8.485 (2.3376)	8.513 (2.2303)	8.416 (2.4390)	8.609 (2.1298)
Day 4	7.821 (2.4482)	7.695 (2.5130)	7.723 (2.7156)	7.761 (2.5058)
Day 5	6.983 (2.7284)	6.979 (2.5706)	7.013 (2.7490)	6.917 (2.6312)
Day 6	6.323 (2.7807)	6.203 (2.8719)	6.315 (2.7980)	6.039 (2.7838)
Day 7	5.528 (2.9747)	5.538 (2.7449)	5.576 (2.8508)	5.126 (2.7096)
Day 8	4.766 (2.8631)	4.750 (2.6755)	4.891 (2.7598)	4.387 (2.6004)
Day 9	4.204 (2.8149)	4.322 (2.7254)	4.445 (2.7381)	3.839 (2.5924)
Day 10	3.634 (2.6815)	3.763 (2.6391)	3.845 (2.6634)	3.404 (2.6805)
Day 11	3.051 (2.5229)	3.284 (2.6658)	3.256 (2.5716)	2.843 (2.6469)
Day 12	2.609 (2.5200)	2.754 (2.5680)	2.756 (2.3795)	2.413 (2.5608)
Day 13	2.038 (2.4202)	2.246 (2.5296)	2.218 (2.4293)	1.943 (2.4174)
Day 14	1.583 (2.3289)	1.941 (2.5375)	1.836 (2.3300)	1.596 (2.3637)
Day 15	1.332 (2.1485)	1.614 (2.4459)	1.634 (2.3178)	1.352 (2.1882)

6. Secondary Outcome

Title	Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set
Description	The MSS combines the 5 most relevant symptoms of rhinosinusitis based on expert clinician recommendations (rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure). The patient rated the severity of each of the five symptoms of the MSS using a four-point rating scale of increasing severity (0 = none/not present, 1 = mild, 2 = moderate, 3 = severe). The MSS is then the sum of single ratings with a possible range from 0 to 15. Mean change from baseline in the daily Major Symptom Score (MSS) over the entire treatment period was calculated as the average total score from Day 2 to 15 compared to Baseline (Day 1). Negative change from baseline means improvement.
Time Frame	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15

Outcome Measure Data

Analysis Population Description

Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	213	215	212	207
Day 1 (Baseline)	9.657 (1.1201)	9.628 (1.0595)	9.698 (1.0319)	9.676 (1.0823)
Day 2	9.080 (2.0160)	8.935 (2.0268)	9.127 (2.0089)	9.068 (2.0278)
Day 3	8.545 (2.2890)	8.395 (2.2583)	8.528 (2.2591)	8.594 (2.1921)
Day 4	7.803 (2.4779)	7.577 (2.5472)	7.816 (2.5849)	7.739 (2.5750)
Day 5	6.962 (2.7401)	6.874 (2.5865)	7.061 (2.6522)	6.821 (2.6717)
Day 6	6.315 (2.7914)	6.093 (2.8809)	6.349 (2.7000)	5.937 (2.8354)
Day 7	5.479 (2.9550)	5.400 (2.7151)	5.604 (2.7800)	4.981 (2.7163)
Day 8	4.685 (2.8250)	4.605 (2.6399)	4.892 (2.7421)	4.237 (2.5914)
Day 9	4.117 (2.7558)	4.181 (2.6773)	4.382 (2.6734)	3.652 (2.5495)
Day 10	3.521 (2.6127)	3.628 (2.5174)	3.741 (2.5507)	3.222 (2.6197)
Day 11	2.934 (2.4039)	3.144 (2.5214)	3.146 (2.4538)	2.705 (2.6042)
Day 12	2.493 (2.3485)	2.572 (2.3785)	2.608 (2.2228)	2.300 (2.4902)
Day 13	1.897 (2.2146)	2.065 (2.2949)	2.085 (2.2013)	1.816 (2.3077)
Day 14	1.432 (2.0812)	1.749 (2.2779)	1.708 (2.1128)	1.444 (2.2198)
Day 15	1.221 (1.9530)	1.409 (2.1312)	1.524 (2.0846)	1.193 (1.9636)

7. Secondary Outcome

Title	Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set
Description	SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL.
Time Frame	Baseline (Day 1), Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	235	236	238	230
Day 1 (Baseline)	37.8 (16.89)	36.3 (15.82)	36.7 (16.21)	36.3 (17.00)
Day 7	23.6 (15.01)	21.2 (13.14)	22.3 (13.95)	21.1 (13.56)
Day 14	7.2 (10.80)	6.9 (11.15)	7.0 (10.07)	6.5 (10.28)

8. Secondary Outcome

Title	Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set
Description	SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL.
Time Frame	Baseline (Day 1), Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	213	215	212	207
Day 1 (Baseline)	37.7 (16.64)	36.7 (15.89)	36.4 (15.86)	36.2 (16.88)
Day 7	23.3 (14.92)	21.2 (13.32)	22.2 (14.27)	21.0 (13.78)
Day 14	6.9 (10.49)	7.1 (11.43)	6.8 (9.67)	6.6 (10.50)

9. Secondary Outcome

Title	Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set
Description	SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome.
Time Frame	Baseline (Day 1), Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	235	236	238	230
Day 7	-35.8 (33.25)	-38.2 (37.48)	-36.7 (34.61)	-39.6 (30.42)
Day 14	-79.3 (31.27)	-78.9 (31.11)	-78.6 (30.53)	-81.5 (26.54)

10. Secondary Outcome

Title	Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set
Description	SNOT-22 Questionnaire is a disease specific Health-Related Quality of Life (HRQoL) measure that comprises a list of 22 symptoms and social or emotional consequences of the nasal disorder. Every participant is asked to rate how severe each problem had been on a scale from 0 (no problem) to 5 (problem as bad as it can be). The total score is the sum of the scores for all 22 items, ranging from 0 to 110, with a lower score indicating better HRQoL. A negative change from baseline in SNOT-22 is considered a favorable outcome.
Time Frame	Baseline (Day 1), Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	213	215	212	207
Day 7	-36.4 (32.64)	-39.5 (36.68)	-36.7 (33.44)	-39.6 (30.60)
Day 14	-79.8 (30.90)	-78.6 (31.77)	-79.1 (30.16)	-81.0 (27.10)

11. Secondary Outcome

Title	Number of Responders and Non-responders to Treatment, Full Analysis Set
Description	Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.
Time Frame	Day 4, 7, 10 and 15

Outcome Measure Data

Analysis Population Description

Full-Analysis Set (FAS) included all randomized patients who received at least one dose of the trial medication and who had at least one post-baseline assessment of MSS during the double-blind treatment period.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	235	236	238	230
Responders	148 63%	152 63.9%	151 63.4%	150 64.4%
Non-responders	85 36.2%	83 34.9%	86 36.1%	79 33.9%
Responders	209 88.9%	206 86.6%	212 89.1%	209 89.7%
Non-responders	23 9.8%	29 12.2%	15 6.3%	18 7.7%
Responders	225 95.7%	225 94.5%	230 96.6%	219 94%
Non-responders	6 2.6%	7 2.9%	5 2.1%	6 2.6%
Responders	230 97.9%	226 95%	230 96.6%	224 96.1%
Non-responders	4 1.7%	6 2.5%	8 3.4%	4 1.7%

12. Secondary Outcome

Title	Number of Responders and Non-responders to Treatment, Per-Protocol Set
Description	Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.
Time Frame	Day 4, 7, 10 and 15

Outcome Measure Data

Analysis Population Description

Per-Protocol Set (PPS) included all FAS-evaluable patients who completed the double-blind treatment period without major protocol violations that could affect the efficacy evaluation.

Arm/Group Title	Group A: 600 mg Acetylcysteine	Group B: 1200 mg Acetylcysteine	Group C: 2400 mg Acetylcysteine	Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)	four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
Measure Participants	213	215	212	207
Responders	138 58.7%	140 58.8%	132 55.5%	134 57.5%
Non-responders	75 31.9%	75 31.5%	80 33.6%	73 31.3%
Responders	192 81.7%	190 79.8%	191 80.3%	192 82.4%
Non-responders	21 8.9%	25 10.5%	21 8.8%	15 6.4%
Responders	207 88.1%	210 88.2%	209 87.8%	202 86.7%
Non-responders	6 2.6%	5 2.1%	3 1.3%	5 2.1%
Responders	211 89.8%	210 88.2%	206 86.6%	205 88%
Non-responders	2 0.9%	5 2.1%	6 2.5%	2 0.9%

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment up to maximum duration of 22 days.
Adverse Event Reporting Description	Any signs or symptoms were collected from first dose of study treatment up to maximum duration of 22 days.
Arm/Group Title	Group A: 600 mg Acetylcysteine		Group B: 1200 mg Acetylcysteine		Group C: 2400 mg Acetylcysteine		Group D: Placebo
Arm/Group Description	one tablet test product plus three tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)		two tablets test product plus two tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)		four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)		four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily).
All Cause Mortality
	Group A: 600 mg Acetylcysteine		Group B: 1200 mg Acetylcysteine		Group C: 2400 mg Acetylcysteine		Group D: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/235 (0%)		0/238 (0%)		0/238 (0%)		0/233 (0%)
Serious Adverse Events
	Group A: 600 mg Acetylcysteine		Group B: 1200 mg Acetylcysteine		Group C: 2400 mg Acetylcysteine		Group D: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Injury, poisoning and procedural complications
Concussion	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Hand fracture	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Tibia fracture	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Nervous system disorders
Subarachnoid haemorrhage	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Other (Not Including Serious) Adverse Events
	Group A: 600 mg Acetylcysteine		Group B: 1200 mg Acetylcysteine		Group C: 2400 mg Acetylcysteine		Group D: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/235 (3.8%)		15/238 (6.3%)		15/238 (6.3%)		8/233 (3.4%)
Ear and labyrinth disorders
Ear congestion	0/235 (0%)		2/238 (0.8%)		0/238 (0%)		0/233 (0%)
Gastrointestinal disorders
Abdominal distension	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Abdominal pain upper	1/235 (0.4%)		2/238 (0.8%)		1/238 (0.4%)		0/233 (0%)
Diarrhoea	1/235 (0.4%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Dyspepsia	0/235 (0%)		3/238 (1.3%)		2/238 (0.8%)		0/233 (0%)
Nausea	1/235 (0.4%)		0/238 (0%)		1/238 (0.4%)		1/233 (0.4%)
General disorders
Asthenia	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Pyrexia	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Infections and infestations
Acute sinusitis	1/235 (0.4%)		1/238 (0.4%)		1/238 (0.4%)		1/233 (0.4%)
COVID-19	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Otitis media bacterial	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Pulpitis dental	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Sinusitis bacterial	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Investigations
Gamma-glutamyltransferase increased	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Hepatic enzyme increased	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		1/233 (0.4%)
Human chorionic gonadotropin increased	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Nervous system disorders
Headache	2/235 (0.9%)		1/238 (0.4%)		2/238 (0.8%)		1/233 (0.4%)
Respiratory, thoracic and mediastinal disorders
Cough	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Epistaxis	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Nasal crusting	0/235 (0%)		0/238 (0%)		0/238 (0%)		1/233 (0.4%)
Nasal obstruction	1/235 (0.4%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Productive cough	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Rhinitis allergic	1/235 (0.4%)		0/238 (0%)		1/238 (0.4%)		1/233 (0.4%)
Rhinorrhoea	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/235 (0.4%)		0/238 (0%)		0/238 (0%)		0/233 (0%)
Erythema	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Rash	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)
Vascular disorders
Hypertension	0/235 (0%)		1/238 (0.4%)		0/238 (0%)		0/233 (0%)
Hypertensive crisis	0/235 (0%)		0/238 (0%)		1/238 (0.4%)		0/233 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.