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

• ClinicalTrials.gov Identifier: NCT02088216
• Recruitment Status: Completed
• First Posted: March 14, 2014
• Results First Posted: February 18, 2019
• Last Update Posted: March 14, 2019
• Sponsor: Qilu Hospital of Shandong University
• Information provided by (Responsible Party): Qian Qi, Qilu Hospital of Shandong University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non-Cystic Fibrosis Bronchiectasis	Drug: N-acetylcysteine; Other: On-demand treatment	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of N-acetylcysteine on Exacerbations of Bronchiectasis (BENE): a Randomized Controlled Trial
• Actual Study Start Date: April 1, 2014
• Actual Primary Completion Date: December 1, 2017
• Actual Study Completion Date: March 30, 2018

Arms and Interventions

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
Control group; Participants received as-needed therapy.	Other: On-demand treatment; receive as-needed therapy

Outcome Measures

Primary Outcome Measures :

1. Median Number of Exacerbations [ Time Frame: 12 months ]
   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).

Secondary Outcome Measures :

1. Change of Volume of Sputum From Baseline Parameters After the 12-month Follow-up. [ Time Frame: 12 months ]
   The change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
2. Change of Number of Patients With a Positive Sputum Culture for Pseudomonas Aeruginosa [ Time Frame: 12 months ]
   The values in the table were calculated as the value at baseline minus the value at 12 months.
3. Change of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores From Baselines [ Time Frame: 12 months ]

   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.

4. Change in Percentage of Predicted Forced Expiratory Volume in One Second (FEV1%) From Baselines [ Time Frame: 12 months ]
   The change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
5. Change of Forced Expiratory Volume in One Second (FEV1) (L) From Baselines [ Time Frame: 12 months ]
   The change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
6. Change of Forced Vital Capacity (FVC) From Baselines [ Time Frame: 12 months ]
   The change was calculated from two time points as the value at the later time point minus the value at the earlier time point.
7. Time to the First Exacerbation [ Time Frame: 12 months ]
8. Time to Recurrent Exacerbations [ Time Frame: 12 months ]
9. Nature of Sputum (Number of Patients With Yellow Purulent) [ Time Frame: 12 months ]
10. Adverse Events (AEs) (Elevation of Liver Enzymes) [ Time Frame: 12 months ]

Eligibility Criteria

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

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.

Contacts and Locations

Locations

China, Shandong

Qilu Hospital of Shandong University

Jinan, Shandong, China, 250012

Sponsors and Collaborators

Qilu Hospital of Shandong University

Investigators

• Study Director: Yu Li, Professor; Director

  Study Documents (Full-Text)

Documents provided by Qian Qi, Qilu Hospital of Shandong University:

Study Protocol  [PDF] November 2, 2018

Statistical Analysis Plan  [PDF] November 2, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Qian Qi, assistant director, Qilu Hospital of Shandong University
• ClinicalTrials.gov Identifier: NCT02088216
• Other Study ID Numbers: NCFB-FLS-01
• First Posted: March 14, 2014
• Results First Posted: February 18, 2019
• Last Update Posted: March 14, 2019
• Last Verified: December 2017

Keywords provided by Qian Qi, Qilu Hospital of Shandong University:

N-acetylcysteine； Bronchiectasis； Acute exacerbations； Antioxidant； Anti-inflammatory

Additional relevant MeSH terms:

Bronchiectasis; Bronchial Diseases; Respiratory Tract Diseases; Acetylcysteine; N-monoacetylcystine; Antiviral Agents; Anti-Infective Agents; Expectorants; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Antidotes