Clinical trial NCT02088216: Effect of Long-term, High-dose N-acetylcysteine on Exacerbations of Bronchiectaisis
Official title: Effect of N-acetylcysteine on Exacerbations of Bronchiectasis (BENE): a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Cystic Fibrosis Bronchiectasis
Keywords: N-acetylcysteine；
Bronchiectasis；
Acute exacerbations；
Antioxidant；
Anti-inflammatory
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2014-03-14
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Median Number of Exacerbations
timeFrame: 12 months
Secondary outcomes:
measure: Change of Volume of Sputum From Baseline Parameters After the 12-month Follow-up.
timeFrame: 12 months
measure: Change of Number of Patients With a Positive Sputum Culture for Pseudomonas Aeruginosa
timeFrame: 12 months
measure: Change of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores From Baselines
timeFrame: 12 months
measure: Change in Percentage of Predicted Forced Expiratory Volume in One Second (FEV1%) From Baselines
timeFrame: 12 months
measure: Change of Forced Expiratory Volume in One Second (FEV1) (L) From Baselines
timeFrame: 12 months
measure: Change of Forced Vital Capacity (FVC) From Baselines
timeFrame: 12 months
measure: Time to the First Exacerbation
timeFrame: 12 months
measure: Time to Recurrent Exacerbations
timeFrame: 12 months
measure: Nature of Sputum (Number of Patients With Yellow Purulent)
timeFrame: 12 months
measure: Adverse Events (AEs) (Elevation of Liver Enzymes)
timeFrame: 12 months
Other outcomes:
Locations:
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
Study officials:
affiliation: Director
name: Yu Li, Professor
role: STUDY_DIRECTOR
References:
citation: 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.