Effect of Long-term, High-dose N-acetylcysteine on Exacerbations of Bronchiectaisis

Study Overview
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Brief Summary
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Objective: To evaluate whether long-term oral N-acetylcysteine as an expectorant drug can reduce the frequency of acute exacerbations of patients with non-cystic fibrosis bronchiectasis and improve their quality of life. Methods: Patients with non-cystic fibrosis bronchiectasis will be randomly assigned to the observer group (participants receive 600 mg of oral N-acetylcysteine BID for 12 months) or the control group (participants receive oral tablet BID for 12 months). The primary endpoint was the frequency of acute exacerbations. Expected results: Compared with the control group, the frequency of acute exacerbations of the observer Group will decrease significantly. Hypothesis: Long-term oral N-acetylcysteine can reduce the frequency of acute exacerbations of patients with non-cystic fibrosis bronchiectasis and improve their quality of life.

Detailed Description
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Objective: N-acetylcysteine is a classic mucolytic agent. This study aimed to investigate the efficacy and safety of N-acetylcysteine on the risk of exacerbations in bronchiectasis patients. Methods: A prospective, randomized, controlled trial was conducted between April 1, 2014 and December 31, 2016 in five general hospitals in Shandong Province, China. Adult bronchiectasis patients with at last two exacerbations in the past year were potentially eligible. Patients were randomly assigned to receive oral N-acetylcysteine (600 mg, twice daily, 12 months) or on-demand treatment. Results: A total of 161 patients were eligible for randomization (81 to the N-acetylcysteine group and 80 to the control group). During the 12-month follow-up, the incidence of exacerbations in the N-acetylcysteine group was significantly lower than that in the control group (1.31 vs. 1.98 exacerbations per patient-year; risk ratio, 0.41; 95% CI, 0.17-0.66; P = 0.0011). The median number of exacerbations in the N-acetylcysteine group was 1 (0.5-2), compared with 2 (1-2) in the control group (U=-2.95, P = 0.003). No severe adverse events were reported in the intervention group. Conclusion: The long-term use of N-acetylcysteine is able to reduce the risk of exacerbations for bronchiectasis patients.

Official Title
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Effect of N-acetylcysteine on Exacerbations of Bronchiectasis (BENE): a Randomized Controlled Trial

Conditions
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Non-Cystic Fibrosis Bronchiectasis

Intervention / Treatment
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* Drug: N-acetylcysteine
* Other: On-demand treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects were aged 18-80 years old; a diagnosis of idiopathic or post-infective bronchiectasis was made; patients had at least two exacerbations in the past year and were in a stable state for at least 4 weeks prior to the primary enrollment. Exclusion Criteria: Patients were excluded if they fulfilled any of the following criteria: current smokers; cigarette smoking within 6 months; cystic fibrosis or other etiologies (such as immunodeficiency, allergic bronchopulmonary aspergillosis, traction bronchiectasis caused by emphysema, advanced pulmonary fibrosis, etc.); pulmonary function test results showing a forced expiratory volume in 1 s (FEV1) ≤ 30% of the predicted value; a history of severe cardiovascular or neurological disease; comorbidity with liver disease, kidney disease, malignant tumor, gastric ulcer, or intestinal malabsorption; a known allergy to N-acetylcysteine; pregnancy or lactation (for women); a history of prior macrolide use of more than 1 week; and poor compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: N-Acetylcysteine group<br>Participants received 600 mg of oral N-acetylcysteine BID for 12 months. | Drug: N-acetylcysteine<br>* 600mg po twice a day for 12 months<br>|
| Other: Control group<br>Participants received as-needed therapy. | Other: On-demand treatment<br>* receive as-needed therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Number of Exacerbations | An exacerbation of bronchiectasis is defined as either a change in one or more of the common symptoms of bronchiectasis (sputum volume or purulence, dyspnea, cough, and fatigue/malaise) or the onset of new symptoms (fever, pleurisy, haemoptysis or need for antibiotic treatment). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Volume of Sputum From Baseline Parameters After the 12-month Follow-up. | The change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | 12 months | 
| Change of Number of Patients With a Positive Sputum Culture for Pseudomonas Aeruginosa | The values in the table were calculated as the value at baseline minus the value at 12 months. | 12 months | 
| Change of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores From Baselines | Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores: the minimum value is 0 and the maximum value is 40. 0-10 points: slight impact; 11-20 points: medium impact; 21-30 points: serious impact; 31-40 points: very serious impact. The change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | 12 months | 
| Change in Percentage of Predicted Forced Expiratory Volume in One Second (FEV1%) From Baselines | The change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | 12 months | 
| Change of Forced Expiratory Volume in One Second (FEV1) (L) From Baselines | The change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | 12 months | 
| Change of Forced Vital Capacity (FVC) From Baselines | The change was calculated from two time points as the value at the later time point minus the value at the earlier time point. | 12 months | 
| Time to the First Exacerbation |  | 12 months | 
| Time to Recurrent Exacerbations |  | 12 months | 
| Nature of Sputum (Number of Patients With Yellow Purulent) |  | 12 months | 
| Adverse Events (AEs) (Elevation of Liver Enzymes) |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetylcysteine；, Bronchiectasis；, Acute exacerbations；, Antioxidant；, Anti-inflammatory