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

Non-Cystic Fibrosis Bronchiectasis Clinical Trial

— BENE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02088216
• Other study ID #: NCFB-FLS-01
• Status: Completed
• Phase: N/A
• Start date: April 1, 2014
• Est. completion date: March 30, 2018

Study information

• Verified date: December 2017
• Source: Qilu Hospital of Shandong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: March 30, 2018
• Est. primary completion date: December 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiectasis
• Non-Cystic Fibrosis Bronchiectasis

Intervention

Drug:
• N-acetylcysteine
600mg po twice a day for 12 months

Other:
• On-demand treatment
receive as-needed therapy

Locations

Country	Name	City	State
China	Qilu Hospital of Shandong University	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Hospital of Shandong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to the First Exacerbation		12 months
Secondary	Time to Recurrent Exacerbations		12 months
Secondary	Nature of Sputum (Number of Patients With Yellow Purulent)		12 months
Secondary	Adverse Events (AEs) (Elevation of Liver Enzymes)		12 months