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
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
1 other identifier
interventional
333
1 country
32
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2019
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 13, 2019
CompletedFirst Posted
Study publicly available on registry
February 18, 2019
CompletedStudy Start
First participant enrolled
June 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 23, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 5, 2021
CompletedResults Posted
Study results publicly available
January 5, 2023
CompletedSeptember 5, 2025
September 1, 2025
1.6 years
February 13, 2019
January 20, 2022
September 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo
The superiority of slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum viscosity score was demonstrated. Sputum viscosity was assessed by ordinal categorical 4-point scales \[0 = Liquid (normal viscosity), 1= Fluid (mildly increased viscosity), 2 = Viscous (moderately increased viscosity), 3 = Sticky (severely increased viscosity)\] with 0 = best and 3= worst.
From baseline upto Day 7
Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo
The superiority of slow intravenous infusion of NAC 600 mg twice daily to placebo in terms of change from baseline in expectoration difficulty score was demonstrated. Expectoration difficulty was assessed by ordinal categorical 4-point scales \[0 = No difficulty, 1 = Mild difficulty, 2 = Moderate difficulty, 3 = Marked difficulty\] with 0 = best and 3 = worst.
From Baseline upto Day 7
Secondary Outcomes (12)
Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo
From Baseline to Day 3
Change From Baseline to Day 3 in Mean Expectoration Difficulty Score of NAC and Placebo
From Baseline to Day 3
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of NAC and Placebo
From Baseline upto Day 3 and Day 7
Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of NAC and Placebo
From Baseline upto Day 3 and Day 7
Change From Baseline to Day 3 and to Day 7 of Mean Sputum Volume of NAC and Placebo
From Baseline upto Day 3 and Day 7
- +7 more secondary outcomes
Other Outcomes (1)
Number of Participants With Adverse Events
From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]
Study Arms (3)
Active test treatment-NAC
EXPERIMENTALNAC 600mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Active control treatment-Ambroxol hydrochloride
ACTIVE COMPARATORAmbroxol hydrochloride 30 mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Placebo
PLACEBO COMPARATORPlacebo will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Interventions
NAC will be administered twice a day, morning and evening, during treatment period.
Ambroxol hydrochloride will be administered twice a day, morning and evening, during treatment period.
Placebo will be administered twice a day, morning and evening, during treatment period.
Eligibility Criteria
You may qualify if:
- 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.
- Chinese ethnicity and/or Chinese
- Signed the informed consent form before any study-related procedure
- Sputum viscosity score ≥ 2 at randomization visit
- Expectoration difficulty score ≥ 2 at randomization visit
- Willingness and ability to comply with study procedures
You may not qualify if:
- Intolerance or contra-indication to treatment with NAC or ambroxol or allergy to any component of the study treatments
- (For female patients) ongoing pregnancy or lactation, or childbearing potential but unwillingness to adopt abstinence or contraception measures during the study
- Intake of an investigational drug within 1 month before the screening visit
- Use of expectorants or drugs with expectorant effect within 2 days before randomization visit
- 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
- 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
- Serum alanine aminotransferase and/or aspartate transaminase more than 3 times above the upper limit of normal at screening visit
- Serum creatinine more than 3 times above the upper limit of normal at screening visit
- Addiction to alcohol or drugs
- Mental illness, or other reasons for non-cooperation in the investigator's opinion
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Zambon SpAlead
Study Sites (32)
Wuxi Peoples' Hospital affiliated to Nanjing Medical University
Wuxi, No. 299, Qing Yang Rd., Wuxi City, Jiangsu, China
Inner Mongolia Baogang Hospital
Baotou, China
Beijing Hospital
Beijing, China
Beijing Tongren Hospital
Beijing, China
China-Japan Friendship Hospital
Beijing, China
Peking University Shougang Hospital
Beijing, China
Jilin Province People's Hospital
Changchun, China
The First Bethune Hospital of Jilin University
Changchun, China
Chengdu Fifth People's Hospital
Chengdu, China
West China Hospital, Sichuan University
Chengdu, China
The First Affiliated Hospital of Chongqing Medical University
Chongqing, China
Deyang People's Hospital
Deyang, China
Inner Mongolia People's Hospital
Hohhot, China
Jinhua city central hospital/Jinhua hospital ,School of Medicine,Zhejiang UNIVERSITY
Jinhua, China
Nanchang University-The Second Affiliated Hospital
Nanchang, China
Nanjing First Hospital
Nanjing, China
Zhongda Hospital, Southeast University - Pulmonology
Nanjing, China
Jiangxi Pingxiang People's Hospital
Pingxiang, China
Qingdao Municipal Hospital
Qingdao, China
Minhang District Central Hospital
Shanghai, China
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, China
Shanghai General Hospital
Shanghai, China
Shanghai Pulmonary Hospital
Shanghai, China
Suining Central Hospital
Suining, China
First Hospital of Shanxi Medical University
Taiyuan, China
The First Hospital of Shanxi Medical University
Taiyuan, China
Tongji Hospital, Tongji Medical College of Huazhong University Science and Technology
Wuhan, China
Wuxi Peoples' Hospital affiliated to Nanjing Medical University
Wuxi, China
Yangzhou First People's Hospital
Yangzhou, China
General Hospital of Ningxia Medical University
Yinchuan, China
Affiliated Hospital of Guangdong Medical University - Respiration
Zhanjiang, China
The First People's Hospital of Zigong
Zigong, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Valentina Zanin
- Organization
- Zambon S.p.A.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Masking Details
- Both rater and patient will be blinded.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 13, 2019
First Posted
February 18, 2019
Study Start
June 25, 2019
Primary Completion
January 23, 2021
Study Completion
February 5, 2021
Last Updated
September 5, 2025
Results First Posted
January 5, 2023
Record last verified: 2025-09