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

Rhinosinusitis Clinical Trial

Official title:

Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis: a Prospective, Randomized, Double-blind, Placebo-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04123405
• Other study ID #: 2018-08-EFT-1
• Secondary ID: 2019-000060-20
• Status: Completed
• Phase: Phase 3
• Start date: October 22, 2020
• Est. completion date: April 20, 2021

Study information

• Verified date: October 2021
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 944
• Est. completion date: April 20, 2021
• Est. primary completion date: April 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 75 Years

Eligibility

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

3. 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:

1. Analgesics

2. Non-steroidal anti-inflammatory drugs

3. Antihistamines

15. Concomitant use of intranasal saline irrigation

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

17. Immunocompromised state

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

19. Pregnant or breast-feeding female patient

20. 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

21. 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

22. 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

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

24. Use of snuff tobacco

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

26. 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.

Related Conditions & MeSH terms

• Rhinosinusitis
• Sinusitis

Intervention

Drug:
• acetylcysteine
600 mg tablet
• Placebo
Placebo to acetylcysteine

Locations

Country	Name	City	State
Bulgaria	Sandoz Investigative Site	Burgas
Bulgaria	Sandoz Investigative Site	Gabrovo
Bulgaria	Sandoz Investigative Site	Plovdiv
Bulgaria	Sandoz Investigative Site	Sliven
Bulgaria	Sandoz Investigative Site	Sofia
Bulgaria	Sandoz Investigative Site	Sofia
Bulgaria	Sandoz Investigative Site	Sofia
Bulgaria	Sandoz Investigative Site	Sofia
Bulgaria	Sandoz Investigative Site	Yambol
Germany	Sandoz Investigative Site	Aachen
Germany	Sandoz Investigative Site	Dresden
Germany	Sandoz Investigative Site	Duisburg
Moldova, Republic of	Sandoz Investigative Site	Chi?inau
Moldova, Republic of	Sandoz Investigative Site	Chi?inau
Moldova, Republic of	Sandoz Investigative Site	Chi?inau
Moldova, Republic of	Sandoz Investigative Site	Chi?inau
Moldova, Republic of	Sandoz Investigative Site	Chi?inau
Moldova, Republic of	Sandoz Investigative Site	Chi?inau
Moldova, Republic of	Sandoz Investigative Site	Orhei
Russian Federation	Sandoz Investigative Site	Kazan
Russian Federation	Sandoz Investigative Site	Kemerovo
Russian Federation	Sandoz Investigative Site	Moscow
Russian Federation	Sandoz Investigative Site	Moscow
Russian Federation	Sandoz Investigative Site	Moscow
Russian Federation	Sandoz Investigative Site	Moscow
Russian Federation	Sandoz Investigative Site	Novosibirsk
Russian Federation	Sandoz Investigative Site	Ryazan
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Saint Petersburg
Russian Federation	Sandoz Investigative Site	Smolensk
Russian Federation	Sandoz Investigative Site	St. Petersburg
Russian Federation	Sandoz Investigative Site	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
Sandoz

Countries where clinical trial is conducted

Bulgaria,  Germany,  Moldova, Republic of,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set	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.	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Primary	Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set	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.	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Secondary	Time to Onset of Action, Full Analysis Set	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.	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Secondary	Time to Onset of Action, Per-Protocol Set	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.	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Secondary	Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set	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.	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Secondary	Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set	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.	Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Secondary	Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set	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.	Baseline (Day 1), Day 7 and Day 14
Secondary	Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set	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.	Baseline (Day 1), Day 7 and Day 14
Secondary	Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set	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.	Baseline (Day 1), Day 7 and Day 14
Secondary	Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set	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.	Baseline (Day 1), Day 7 and Day 14
Secondary	Number of Responders and Non-responders to Treatment, Full Analysis Set	Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.	Day 4, 7, 10 and 15
Secondary	Number of Responders and Non-responders to Treatment, Per-Protocol Set	Number of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator were reported.	Day 4, 7, 10 and 15