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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Drug: N-acetylcysteine; Other: On-demand treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. subjects were aged 18-80 years old;
2. a diagnosis of idiopathic or post-infective bronchiectasis was made;
3. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Study Director: Yu Li, Professor, Director

Publications and helpful links

General Publications

• Qi Q, Ailiyaer Y, Liu R, Zhang Y, Li C, Liu M, Wang X, Jing L, Li Y. Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Respir Res. 2019 Apr 11;20(1):73. doi: 10.1186/s12931-019-1042-x.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): March 30, 2018

Study Registration Dates

• First Submitted: March 5, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 14, 2019
• Last Update Submitted That Met QC Criteria: February 16, 2019
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Anti-inflammatory; N-acetylcysteine；; Bronchiectasis；; Acute exacerbations；; Antioxidant；
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: NCFB-FLS-01