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

Phase 3

Completed

Conditions: Respiratory Tract Diseases
Abnormal Mucus Secretions

Interventions: Drug: N-acetylcysteine (NAC) 600 mg
Drug: Ambroxol hydrochloride 30 mg
Other: placebo

Registration Number: NCT03843541

Lead Sponsor: Zambon SpA

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 333

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active test treatment-NAC	N-acetylcysteine (NAC) 600 mg	NAC 600mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Active control treatment-Ambroxol hydrochloride	Ambroxol hydrochloride 30 mg	Ambroxol hydrochloride 30 mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Placebo	placebo	Placebo will be administered by slow intravenous infusion twice daily for the 1-week treatment period.

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo	From baseline upto Day 7	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.
Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo	From Baseline upto Day 7	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Day 3 in Mean Expectoration Difficulty Score of NAC and Placebo	From Baseline to Day 3	The superiority of slow intravenous infusion of NAC 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.
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	The superiority of the slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum color score was demonstrated. Sputum color was assessed by means of ordinal categorical 4-point scales \[0 = Mostly white, 1= Mostly pale yellow, 2 = Mostly dark yellow, 3 = Very dark yellow /green\] with 0 = best and 3= worst.
Change From Baseline to Day 7 in Mean Sputum Viscosity Score of NAC and Ambroxol Hydrochloride	From baseline upto Day 7	The non-inferiority of NAC versus ambroxol in terms of change from baseline to Day 7 of mean 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.
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Viscosity Score of Ambroxol Hydrochloride and Placebo	From Baseline upto Day 3 and Day 7	The superiority of the slow intravenous infusion ambroxol hydrochloride 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.
Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo	From Baseline to Day 3	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.
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	The superiority of the slow intravenous infusion of NAC to placebo in terms of change from baseline in cough score was demonstrated. Cough score was assessed by means of ordinal categorical 4-point scales \[0 = No cough, 1= Sporadic and mild cough, 2 = Moderate cough, 3 = Severe Cough\] with 0 = best and 3= worst.
Change From Baseline to Day 7 in Mean Expectoration Difficulty Score of NAC and Ambroxol Hydrochloride	From Baseline upto Day 7	The non-inferiority of NAC versus ambroxol in terms of change from baseline to Day 7 of mean 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
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of Ambroxol Hydrochloride and Placebo	From Baseline upto Day 3 and Day 7	The superiority of slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in sputum color was demonstrated. Sputum color was assessed by means of ordinal categorical 4-point scales \[0 = Mostly white, 1= Mostly pale yellow, 2 = Mostly dark yellow, 3 = Very dark yellow /green\] with 0 = best and 3= worst.
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	The superiority of the slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum volume was demonstrated. Patients collected 24-hour sputum (morning to same time of the following morning) in a graduated cup and volume was expressed as mL/24h.
Change From Baseline to Day 3 and to Day 7 in Mean Expectoration Difficulty Score of Ambroxol Hydrochloride and Placebo	From Baseline upto Day 3 and Day 7	The superiority of the slow intravenous infusion of ambroxol hydrochloride 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.
Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of Ambroxol Hydrochloride and Placebo	From Baseline upto Day 3 and Day 7	The superiority of slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in cough score was demonstrated. Cough score was assessed by means of ordinal categorical 4-point scales \[0 = No cough, 1= Sporadic and mild cough, 2 = Moderate cough, 3 = Severe Cough\] with 0 = best and 3= worst.
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Volume of Ambroxol Hydrochloride and Placebo	From Baseline upto Day 3 and Day 7	The superiority of slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in mean sputum volume was demonstrated. Patients collected 24-hour sputum (morning to same time of the following morning) in a graduated cup and volume was expressed as mL/24h.

Trial Locations

Locations (31): Wuxi Peoples' Hospital affiliated to Nanjing Medical University
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Wuxi, China
Inner Mongolia Baogang Hospital
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Baotou, China
Beijing Hospital
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Beijing, China
Beijing Tongren Hospital
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Beijing, China
China-Japan Friendship Hospital
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Beijing, China
Peking University Shougang Hospital
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Beijing, China
Jilin Province People's Hospital
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Changchun, China
The First Bethune Hospital of Jilin University
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Changchun, China
Chengdu Fifth People's Hospital
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Chengdu, China
West China Hospital, Sichuan University
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Chengdu, China
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Wuxi Peoples' Hospital affiliated to Nanjing Medical University
🇨🇳Wuxi, China