Chronic Bronchitis, COPD
Conditions
Keywords
COPD, Chronic Bronchitis, N-acetylcysteine
Brief summary
N-acetylcysteine (NAC) is described as having mucolytic and antioxidant properties. It is widely prescribed for patients with chronic obstructive lung disease (COPD), particularly for those who have accompanying symptoms of chronic cough and sputum production. Compared to placebo, high-dose NAC will improve Saint George Respiratory Questionnaire scores in patients with COPD and chronic bronchitis.
Detailed description
A total of 130 subjects with COPD and chronic bronchitis will be randomized (in a double-blind fashion) to receive either high-dose NAC (1800 mg) or matching placebo twice daily for eight weeks. Respiratory health status, assessed by changes in St. George's Respiratory Questionnaire, will be used to determine the effects of NAC on lung function. It is anticipated that the subjects on high dose NAC will have improved scores.
Interventions
DRUGN-Acetylcysteine
1800 mg twice daily for 8 weeks
DRUGPlacebo
Identical placebo manufactured to mimic appearance of intervention drug with identical frequency and duration.
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Capability to provide written informed consent * Age ≥ 40 years and ≤ 85 years * FEV1/FVC ratio (post bronchodilator) \< 70% * FEV1 (post bronchodilator) \< 65% * Presence of chronic cough and sputum production defined as the following: * Presence of chronic cough and sputum will be defined by responses to the first two questions on the SGRQ. Subjects who respond positively to both question 1 (cough) and question 2 (sputum) on the SGRQ as either several days per week or almost every day will be eligible * Current or former smoker with lifetime cigarette consumption of at least 10 pack-years * Negative serum pregnancy test at the baseline visit if patient is a pre-menopausal female (menopause defined as absence of a menstrual cycle in the last 12 months) * Must be fluent in speaking the English language
Exclusion criteria
* Not fully recovered for at least 30 days from a COPD exacerbation characterized by typical symptoms and treated with antibiotics or prednisone * Known allergy or sensitivity to NAC or albuterol * Any patient with unstable cardiac disease * Any patient with a documented history of uncompensated congestive heart failure in the last 2 years * Clinical diagnosis of asthma, bronchiectasis, cystic fibrosis, or severe alpha-1 antitrypsin deficiency * Active lung cancer or history of lung cancer if it has been less than 2 years since lung resection or other treatment. If history of lung cancer, must have no evidence of recurrence in the 2 years preceding the baseline visit. * Undergoing active treatment for malignancy except for hormonal therapy (i.e. prostate cancer, breast cancer) or non-metastatic skin cancer and are not symptomatic * Chronic kidney disease with an estimated GFR of \< 30 ml/min. GFR will be estimated using the Modification of Diet in Renal Disease (MDRD) formula * History of cirrhosis with evidence of portal hypertension (ascites, chronic edema) * Participation in a pulmonary rehabilitation program or completion within past 6 weeks * Prisoners or institutionalized patients * Participation in another study involving an investigational product within 30 days of the baseline visit * Pregnant or breast-feeding patients. * Use of guaifenesin in the last 30 days * Currently on long acting nitrates for angina or heart failure * Abnormalities in screening blood work defined as: * WBC \< 3.0 or \> 15.0 K/cmm * Hemoglobin \< 9.0 or \> 17.0 gm/dl * Platelets \< 75 or \> 400 K/cmm * ALT \> 3 times the upper limit of normal * INR \> 1.5 unless on warfarin therapy * Any concomitant condition that might endanger the patient through participation in the study or interfere with study procedures, as assessed by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Saint George's Respiratory Questionnaire | Baseline to 8 weeks | The St. George's Respiratory Questionnaire (SGRQ) is scored on a scale of 1 to 100 with 100 representing the worst respiratory health status. The instrument is self-administered at baseline and again after 8-weeks of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugar Pill Identical placebo pills twice daily for 8 weeks Placebo pills manufactured to mimic appearance of intervention drug n-acetylcysteine and prescribed with identical frequency and duration.
Placebo: Identical placebo manufactured to mimic appearance of intervention drug with identical frequency and duration. | 22 |
| N-Acetylcysteine 1800 mg twice daily for 8 weeks
N-Acetylcysteine: 1800 mg twice daily for 8 weeks | 23 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Early Trial Termination | 2 | 4 |
Baseline characteristics
| Characteristic | Sugar Pill | N-Acetylcysteine | Total |
|---|---|---|---|
| Age, Continuous | 68.9 Years | 70.1 Years | 69.5 Years |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 19 Participants | 18 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 23 |
| other Total, other adverse events | 9 / 22 | 13 / 23 |
| serious Total, serious adverse events | 2 / 22 | 3 / 23 |
Outcome results
Primary
Changes in the Saint George's Respiratory Questionnaire
The St. George's Respiratory Questionnaire (SGRQ) is scored on a scale of 1 to 100 with 100 representing the worst respiratory health status. The instrument is self-administered at baseline and again after 8-weeks of treatment.
Time frame: Baseline to 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Symptoms | -9.8 units on a scale | Standard Deviation 17.8 |
| Placebo | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Activity | -3.7 units on a scale | Standard Deviation 14.5 |
| Placebo | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Impact | -7.5 units on a scale | Standard Deviation 20.1 |
| Placebo | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Total | -7.1 units on a scale | Standard Deviation 16.1 |
| N-Acetylcysteine | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Total | -3.9 units on a scale | Standard Deviation 12.1 |
| N-Acetylcysteine | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Symptoms | -3.5 units on a scale | Standard Deviation 18.6 |
| N-Acetylcysteine | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Impact | -4.5 units on a scale | Standard Deviation 19.9 |
| N-Acetylcysteine | Changes in the Saint George's Respiratory Questionnaire | Change in SGRQ Activity | -4.0 units on a scale | Standard Deviation 13.6 |
p-value: 0.45Fisher Exact