Efficacy and Safety of Acetylcysteine for the Treatment of Acute Uncomplicated Rhinosinusitis: a Prospective, Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sandoz
- 入组人数
- 944
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set
研究概览
简要总结
The trial was conducted as a prospective, randomized, multinational, multicenter, double-blind study in 4 parallel groups of patients.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged between 14 and 75 years inclusive on the date of consent
- •Diagnosis of acute, uncomplicated rhinosinusitis defined at screening visit 1 and at Visit 2 as:
- •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
- •individual score for facial pain/pressure ≥1 (mild) and ≤2 (moderate)
- •presence of symptoms ≤3 days prior to screening visit
- •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.
排除标准
- •History of hypersensitivity or intolerance to the active substance or any of the excipients of the trial medication
- •Patient with history of hereditary fructose intolerance, galactose intolerance, lactase deficiency or glucose-galactose malabsorption
- •Chronic rhinosinusitis (symptoms lasting longer than 3 months)
- •Subjects who have undergone sinus or nasal surgery for chronic rhinosinusitis in the 6 months prior to screening visit
- •Sinus lavage within 7 days prior to screening visit
- •Odontogenic rhinosinusitis
- •Allergic (perennial or seasonal) rhinitis
- •Bronchial asthma or chronic obstructive pulmonary disease
- •Nasal polyposis or clinically relevant nasal septum deviation
- •Concomitant otitis
- •Intranasal or systemic use of corticosteroids within 30 days prior to screening visit
- •Intranasal or systemic use of antibiotics within 30 days prior to screening visit
- •Use of nasal decongestants within 2 days prior to screening visit
- •Concomitant treatment of common cold-like symptoms within 7 days prior to screening visit with any of the following:
- •Non-steroidal anti-inflammatory drugs
- •Antihistamines
- •Concomitant use of intranasal saline irrigation
- •Use of immunosuppressive agents within 30 days prior to screening visit
- •Immunocompromised state
- •Suspicion for acute bacterial rhinosinusitis (defined as presence of purulence for 3 to 4 days with fever ≥ 38.3°C)
- •Pregnant or breast-feeding female patient
- •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
- •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
- •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
- •Suspected alcohol/ drug dependence or abuse (including heavy smoking: ≥ 20 cigarettes daily)
- •Use of snuff tobacco
- •Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial
- •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.
研究组 & 干预措施
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)
干预措施: acetylcysteine (Drug)
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)
干预措施: Placebo (Drug)
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)
干预措施: acetylcysteine (Drug)
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)
干预措施: Placebo (Drug)
Group C: 2400 mg acetylcysteine
four tablets test product per day (taken as two tablets dissolved in a glass of water, twice daily)
干预措施: acetylcysteine (Drug)
Group D: Placebo
four tablets placebo per day (taken as two tablets dissolved in a glass of water, twice daily)
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Per-Protocol Set
时间窗: 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.
Mean Change From Baseline in the Daily Major Symptom Score (MSS) Over the Entire Treatment Period, Full Analysis Set
时间窗: 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.
次要结局
- 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)
- Sino-Nasal Outcome Test (SNOT-22) by Visit, Per Protocol Set(Baseline (Day 1), Day 7 and Day 14)
- Number of Responders and Non-responders to Treatment, Per-Protocol Set(Day 4, 7, 10 and 15)
- 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)
- 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)
- 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)
- Sino-Nasal Outcome Test (SNOT-22) by Visit, Full Analysis Set(Baseline (Day 1), Day 7 and Day 14)
- Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Full Analysis Set(Baseline (Day 1), Day 7 and Day 14)
- Sino-Nasal Outcome Test (SNOT-22) by Change to Baseline, Per Protocol Set(Baseline (Day 1), Day 7 and Day 14)
- Number of Responders and Non-responders to Treatment, Full Analysis Set(Day 4, 7, 10 and 15)