Clinical trial NCT04123405: Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis
Official title: Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis: a Prospective, Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rhinosinusitis
Keywords: acute uncomplicated rhinosinusitis, acetylcysteine
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
First posted: 2019-10-10
Enrollment: 944
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set
timeFrame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
measure: Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set
timeFrame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
Secondary outcomes:
measure: Time to Onset of Action, Full Analysis Set
timeFrame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
measure: Time to Onset of Action, Per-Protocol Set
timeFrame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
measure: Major Symptom Score (MSS) Development Over the Course of the Study, Full Analysis Set
timeFrame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
measure: Major Symptom Score (MSS) Development Over the Course of the Study, Per-protocol Set
timeFrame: Baseline (Day 1), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15
measure: Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set
timeFrame: Baseline (Day 1), Day 7 and Day 14
measure: Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set
timeFrame: Baseline (Day 1), Day 7 and Day 14
measure: Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set
timeFrame: Baseline (Day 1), Day 7 and Day 14
measure: Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set
timeFrame: Baseline (Day 1), Day 7 and Day 14
measure: Number of Responders and Non-responders to Treatment, Full Analysis Set
timeFrame: Day 4, 7, 10 and 15
measure: Number of Responders and Non-responders to Treatment, Per-Protocol Set
timeFrame: Day 4, 7, 10 and 15
Other outcomes:
Locations:
city: Burgas
country: Bulgaria
facility: Sandoz Investigative Site
city: Gabrovo
country: Bulgaria
facility: Sandoz Investigative Site
city: Plovdiv
country: Bulgaria
facility: Sandoz Investigative Site
city: Sliven
country: Bulgaria
facility: Sandoz Investigative Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigative Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigative Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigative Site
city: Sofia
country: Bulgaria
facility: Sandoz Investigative Site
city: Yambol
country: Bulgaria
facility: Sandoz Investigative Site
city: Aachen
country: Germany
facility: Sandoz Investigative Site
city: Dresden
country: Germany
facility: Sandoz Investigative Site
city: Duisburg
country: Germany
facility: Sandoz Investigative Site
city: Chișinău
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Chișinău
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Chișinău
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Chișinău
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Chișinău
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Chișinău
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Orhei
country: Moldova, Republic of
facility: Sandoz Investigative Site
city: Kazan
country: Russian Federation
facility: Sandoz Investigative Site
city: Kemerovo
country: Russian Federation
facility: Sandoz Investigative Site
city: Moscow
country: Russian Federation
facility: Sandoz Investigative Site
city: Moscow
country: Russian Federation
facility: Sandoz Investigative Site
city: Moscow
country: Russian Federation
facility: Sandoz Investigative Site
city: Moscow
country: Russian Federation
facility: Sandoz Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Sandoz Investigative Site
city: Ryazan
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Smolensk
country: Russian Federation
facility: Sandoz Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Sandoz Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Sandoz Investigative Site
Study officials:
affiliation: Sandoz
name: Sandoz
role: STUDY_DIRECTOR
References: