Clinical trial NCT03843541: A Clinical Trial to Compare the Efficacy and Safety of 1-week Treatment of Intravenous N-acetylcysteine (NAC) 600 mg Twice Daily, Ambroxol Hydrochloride 30 mg Twice Daily and Placebo as Expectorant Therapies in Adult Chinese Patients With Respiratory Tract Diseases and Abnormal Mucus Secretions
Official title: A Phase III, Multi-centre, Randomized, Rater- and Patient-blind, Placebo- and Active-controlled, Parallel Group Clinical Trial to Compare the Efficacy and Safety of 1-week Treatment of Intravenous N-acetylcysteine (NAC) 600 mg Twice Daily (Active Test Treatment), Ambroxol Hydrochloride 30 mg Twice Daily (Active Control Treatment) and Placebo as Expectorant Therapies in Adult Chinese Patients With Respiratory Tract Diseases and Abnormal Mucus Secretions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Tract Diseases
Abnormal Mucus Secretions
Keywords: N-acetylcysteine (NAC)
ambroxol hydrochloride
bronchitis
cystic fibrosis
fibrosis bronchiectasis
increased sputum viscosity
cough
Chronic Obstructive Pulmonary Disease (COPD)
Lead sponsor: Zambon SpA
Sponsor class: INDUSTRY
First posted: 2019-02-18
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: There will be 3 treatment groups of NAC, ambroxol and placebo. A total of 333 patients will be randomized to NAC or ambroxol or placebo in a 1:1:1 ratio. Approximately 111 patients will be randomized in each treatment group.
Primary purpose: TREATMENT

Brief summary: This is a phase 3, multicenter, randomized, rater- and patient-blind, placebo- and active-controlled, 3-arm parallel group clinical trial. Patients will be randomized to N-acetylcysteine (NAC) or ambroxol or placebo in a 1:1:1 ratio. A total of approximately 333 patients in China will be randomized. The total study duration will be approximately 8 months including the enrolment period of approximately 7 months and the patient participation duration of 1 month or 4 weeks. Each patient will undergo a screening period of up to 1 week, a 1-week treatment period and a 2-week follow-up period. This study will be conducted in approximately 15-25 sites in China.


Eligibility criteria: Inclusion Criteria:

1. Male or female adult (≥18 years old) hospitalized patients with respiratory tract diseases and abnormal mucus secretions such as: acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis and bronchiectasis.
2. Chinese ethnicity and/or Chinese
3. Signed the informed consent form before any study-related procedure
4. Sputum viscosity score ≥ 2 at randomization visit
5. Expectoration difficulty score ≥ 2 at randomization visit
6. Willingness and ability to comply with study procedures

Exclusion Criteria:

1. Intolerance or contra-indication to treatment with NAC or ambroxol or allergy to any component of the study treatments
2. (For female patients) ongoing pregnancy or lactation, or childbearing potential but unwillingness to adopt abstinence or contraception measures during the study
3. Intake of an investigational drug within 1 month before the screening visit
4. Use of expectorants or drugs with expectorant effect within 2 days before randomization visit
5. Diagnosis of active tuberculosis, lung cancer, pulmonary fibrosis, acute pulmonary thromboembolism or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the patient or affect the interpretation of the results
6. Medical history of and/or illness (including laboratory abnormality) and/or treatment that in the investigator's opinion may interfere with the patient's safety, compliance, or study evaluations
7. Serum alanine aminotransferase and/or aspartate transaminase more than 3 times above the upper limit of normal at screening visit
8. Serum creatinine more than 3 times above the upper limit of normal at screening visit
9. Addiction to alcohol or drugs
10. Mental illness, or other reasons for non-cooperation in the investigator's opinion

Primary outcomes:
measure: Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo
timeFrame: From baseline upto Day 7
measure: Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo
timeFrame: From Baseline upto Day 7
Secondary outcomes:
measure: Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo
timeFrame: From Baseline to Day 3
measure: Change From Baseline to Day 3 in Mean Expectoration Difficulty Score of NAC and Placebo
timeFrame: From Baseline to Day 3
measure: Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of NAC and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of NAC and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 3 and to Day 7 of Mean Sputum Volume of NAC and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 7 in Mean Sputum Viscosity Score of NAC and Ambroxol Hydrochloride
timeFrame: From baseline upto Day 7
measure: Change From Baseline to Day 7 in Mean Expectoration Difficulty Score of NAC and Ambroxol Hydrochloride
timeFrame: From Baseline upto Day 7
measure: Change From Baseline to Day 3 and to Day 7 in Mean Sputum Viscosity Score of Ambroxol Hydrochloride and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 3 and to Day 7 in Mean Expectoration Difficulty Score of Ambroxol Hydrochloride and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of Ambroxol Hydrochloride and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of Ambroxol Hydrochloride and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
measure: Change From Baseline to Day 3 and to Day 7 in Mean Sputum Volume of Ambroxol Hydrochloride and Placebo
timeFrame: From Baseline upto Day 3 and Day 7
Other outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]
Locations:
city: Wuxi
country: China
facility: Wuxi Peoples' Hospital affiliated to Nanjing Medical University
state: No. 299, Qing Yang Rd., Wuxi City, Jiangsu
city: Baotou
country: China
facility: Inner Mongolia Baogang Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Beijing
country: China
facility: China-Japan Friendship Hospital
city: Beijing
country: China
facility: Peking University Shougang Hospital
city: Changchun
country: China
facility: Jilin Province People's Hospital
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
city: Chengdu
country: China
facility: Chengdu Fifth People's Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
city: Deyang
country: China
facility: Deyang People's Hospital
city: Hohhot
country: China
facility: Inner Mongolia People's Hospital
city: Jinhua
country: China
facility: Jinhua city central hospital/Jinhua hospital ,School of Medicine,Zhejiang UNIVERSITY
city: Nanchang
country: China
facility: Nanchang University-The Second Affiliated Hospital
city: Nanjing
country: China
facility: Nanjing First Hospital
city: Nanjing
country: China
facility: Zhongda Hospital, Southeast University - Pulmonology
city: Pingxiang
country: China
facility: Jiangxi Pingxiang People's Hospital
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
city: Shanghai
country: China
facility: Minhang District Central Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: SuiNing
country: China
facility: Suining Central Hospital
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Huazhong University Science and Technology
city: Wuxi
country: China
facility: Wuxi Peoples' Hospital affiliated to Nanjing Medical University
city: Yangzhou
country: China
facility: Yangzhou First People's Hospital
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University - Respiration
city: Zigong
country: China
facility: The First People's Hospital of Zigong
Study officials:
References: