Non-Cystic Fibrosis Bronchiectasis
Conditions
Keywords
N-acetylcysteine；, Bronchiectasis；, Acute exacerbations；, Antioxidant；, Anti-inflammatory
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.
Interventions
DRUGN-acetylcysteine
600mg po twice a day for 12 months
OTHEROn-demand treatment
receive as-needed therapy
Sponsors
Qilu Hospital of Shandong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Number of Exacerbations | 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
| Measure | Time frame | Description |
|---|---|---|
| Change of Number of Patients With a Positive Sputum Culture for Pseudomonas Aeruginosa | 12 months | The values in the table were calculated as the value at baseline minus the value at 12 months. |
| Change of Forced Expiratory Volume in One Second (FEV1) (L) From Baselines | 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. |
| Change of Forced Vital Capacity (FVC) From Baselines | 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. |
| Time to the First Exacerbation | 12 months | — |
| Change of Volume of Sputum From Baseline Parameters After the 12-month Follow-up. | 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. |
| Change in Percentage of Predicted Forced Expiratory Volume in One Second (FEV1%) From Baselines | 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. |
| 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 | — |
| Change of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores From Baselines | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine Group Participants received oral N-acetylcysteine (600 mg, twice daily, 12 months). | 81 |
| Control Group Participants received on-demand treatment. | 80 |
| Total | 161 |
Baseline characteristics
| Characteristic | N-acetylcysteine Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 53.28 years STANDARD_DEVIATION 11.9 | 56.56 years STANDARD_DEVIATION 12.41 | 54.91 years STANDARD_DEVIATION 12.23 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 45 Participants | 52 Participants | 97 Participants |
| Sex: Female, Male Male | 36 Participants | 28 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 81 | 3 / 80 |
| other Total, other adverse events | 8 / 81 | 6 / 80 |
| serious Total, serious adverse events | 0 / 81 | 0 / 80 |
Outcome results
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).
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| N-acetylcysteine Group | Median Number of Exacerbations | 1 exacerbations |
| Control Group | Median Number of Exacerbations | 2 exacerbations |
Secondary
Adverse Events (AEs) (Elevation of Liver Enzymes)
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N-acetylcysteine Group | Adverse Events (AEs) (Elevation of Liver Enzymes) | 3 Participants |
| Control Group | Adverse Events (AEs) (Elevation of Liver Enzymes) | 0 Participants |
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine Group | Change in Percentage of Predicted Forced Expiratory Volume in One Second (FEV1%) From Baselines | 1.16 percentage of predicted FEV1 | Standard Deviation 16.5 |
| Control Group | Change in Percentage of Predicted Forced Expiratory Volume in One Second (FEV1%) From Baselines | 0.13 percentage of predicted FEV1 | Standard Deviation 7.78 |
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine Group | Change of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores From Baselines | -3.79 score on a scale | Standard Deviation 5.4 |
| Control Group | Change of Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores From Baselines | -1.44 score on a scale | Standard Deviation 6.19 |
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine Group | Change of Forced Expiratory Volume in One Second (FEV1) (L) From Baselines | -0.10 L | Standard Deviation 0.37 |
| Control Group | Change of Forced Expiratory Volume in One Second (FEV1) (L) From Baselines | 0.03 L | Standard Deviation 0.16 |
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine Group | Change of Forced Vital Capacity (FVC) From Baselines | 0.01 L | Standard Deviation 0.46 |
| Control Group | Change of Forced Vital Capacity (FVC) From Baselines | 0.03 L | Standard Deviation 0.22 |
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.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N-acetylcysteine Group | Change of Number of Patients With a Positive Sputum Culture for Pseudomonas Aeruginosa | 8 Participants |
| Control Group | Change of Number of Patients With a Positive Sputum Culture for Pseudomonas Aeruginosa | 5 Participants |
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine Group | Change of Volume of Sputum From Baseline Parameters After the 12-month Follow-up. | -6.46 mL | Standard Deviation 22.93 |
| Control Group | Change of Volume of Sputum From Baseline Parameters After the 12-month Follow-up. | -18.28 mL | Standard Deviation 25.69 |
Secondary
Nature of Sputum (Number of Patients With Yellow Purulent)
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| N-acetylcysteine Group | Nature of Sputum (Number of Patients With Yellow Purulent) | 12 Participants |
| Control Group | Nature of Sputum (Number of Patients With Yellow Purulent) | 31 Participants |
Secondary
Time to Recurrent Exacerbations
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| N-acetylcysteine Group | Time to Recurrent Exacerbations | 313.70 days |
| Control Group | Time to Recurrent Exacerbations | 266.88 days |
Secondary
Time to the First Exacerbation
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| N-acetylcysteine Group | Time to the First Exacerbation | 140 days |
| Control Group | Time to the First Exacerbation | 115 days |