Moxifloxacin in Acute Exacerbations of Chronic Bronchitis
Moxifloxacin in Acute Exacerbations of Chronic Bronchitis
A total of 2672 patients were enrolled in the study and included in the safety population. The efficacy population consisted of 2536 patients, after exclusion of 136 (5.1%) patients from the safety population, most commonly because of age < 35 years (n = 119) (Figure 1).
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Figure 1.
Patient disposition.
Demographic and disease characteristics of the efficacy population at baseline are presented in Table 1. Patient ages ranged from 35 to 94 years, with approximately one-third of patients (31.6%) aged above 65 years. Over one-half of patients (53.9%) were past or current smokers. Over the past 12 months, patients had experienced a mean of 2.7 ± 1.9 (range 1.0–20.0) episodes of AECB. An antibiotic was prescribed for the previous episode of AECB in 62.2% of patients, most commonly amoxicillin (13.6% of patients), usually combined with clavulanic acid.
The most common symptoms in the current AECB episode were increased sputum purulence, worsening of dyspnea, and increased sputum volume (Table 1); 42.9% of patients were classified as Anthonisen type I, 40.2% as type II, and 16.2% as type III, with data missing in the remainder (Table 1). One-half of patients (49.9%) complained of an infection of the upper respiratory tract in the past 5 days. An impact on daily life activities was reported by 90.4%, over a mean duration of 6.6 ± 5.5 days. Sleep disturbances were reported by 68.6% of patients, with impact on a mean of 4.1 ± 3.7 nights. The impact of the current AECB episode on daily activities and sleep disturbance in patient subgroups categorized by gender, age, smoking status, concomitant diseases, Anthonisen grade, and number of severe symptoms is presented in Table 2. Mean FEV1 (measured in 1261 patients) was 2.0 ± 0.9 liters. Patients experienced AECB symptoms for a mean of 7.0 ± 5.0 days before initiation of treatment with moxifloxacin.
Concomitant diseases of special interest recorded by investigators included COPD (66.0% of patients), emphysema (23.8%), asthma (16.6%), cardiac ischemia (23.1%), cor pulmonale (10.6%), and diabetes (10.1%). Concomitant medications were taken by 93.3% of patients, most commonly a corticosteroid (32.8% overall, including 40.8% of Anthonisen type I, 28.0% of type II, and 24.2% of type III patients); the mucolytic ambroxol (18.8%); and the mucolytic/antioxidant, acetylcysteine (18.6%). As expected, a large proportion of patients (83.4%) received comedications to treat their respiratory symptoms.
The most frequently used non-AECB-related comedications were for the treatment of cardiovascular symptoms (36.1% of patients), dermatological diseases (23.0%), dysfunction of the alimentary tract and metabolism (22.2%), and ophthalmological diseases (20.5%).
Moxifloxacin was administered at the recommended dose of 400 mg once daily in 99.6% (n = 2526) of enrolled patients, with a higher dose of 600 mg/day (n = 5) or 800 mg/day (n = 5) in the remainder.
The mean (SD) duration of moxifloxacin treatment was 6.4 ± 1.9 days (range: 1.0–15.0 days) in the efficacy population; 55.2% of patients were treated for 5 days, 29.1% for 7 days, and 14.0% for 10 days. Mean durations of treatment in patients with Anthonisen type I, type II, and type III AECB were 6.4 ± 1.9, 6.4 ± 1.9, and 6.2 ± 1.8 days, respectively, and were 6.3 ± 1.9 days in never smokers versus 6.5 ± 1.9 days in past or current smokers. Durations of treatment were 6.0 ± 1.8 days for patients aged < 50 years, 6.4 ± 1.9 for age ≥ 50 to < 65, 6.7 ± 2.0 days for age ≥ 65 to < 80, and 7.0 ± 1.9 days for age ≥ 80 years.
The last follow-up visit was performed after a mean of 9.8 ± 6.2 days (range 2–66 days) from the initiation of moxifloxacin treatment. Moxifloxacin was discontinued prematurely in 23 (0.9%) patients, because of the patient's decision (n = 4), insufficient efficacy (n = 3), adverse events (n = 9), and 'other reasons' (n = 8) (multiple responses included).
An improvement or relief of the symptoms of AECB that were present at baseline was reported in 89.4% of patients for sputum volume, 97.2% for fever, 86.0% for cough, 87.7% for dyspnea, and 77.2% for sputum character during moxifloxacin treatment. Additional symptom changes are presented in Table 3.
Improvement in symptoms occurred after a mean of 3.4 ± 1.4 days of moxifloxacin treatment. Improvements occurred by 3 days in 60.7% of patients, 5 days in 93.2%, and 10 days in 99.3%. Only 0.6% of patients (n = 14) experienced no symptom improvements during the observational period.
The mean duration of treatment until symptom improvement in patients with Anthonisen type I, II, and III AECB was 3.6 ± 1.5, 3.3 ± 1.4, and 3.4 ± 1.4 days, respectively (Table 4), 3.4 ± 1.4 days in never smokers versus 3.5 ± 1.5 days in past or current smokers, 3.6 ± 1.6 days in concomitant corticosteroid users versus 3.4 ± 1.3 in non-corticosteroid users, and 3.7 ± 1.5 days in patients with >3 exacerbations versus 3.4 ± 1.4 days in patients with ≤3 exacerbations in the previous 12 months. Duration of treatment until symptom improvement was 3.2 ± 1.4 days in patients aged < 50 years, 3.4 ± 1.4 days for age ≥ 50 to < 65, 3.6 ± 1.5 days for age ≥ 65 to < 80, and 3.7 ± 1.9 for age ≥ 80 years. Mean duration of treatment until symptom improvement in patients with concomitant diseases is described in Table 4. For patients with COPD (diagnosed by the attending physician), the mean duration of moxifloxacin treatment until improvement was 3.5 ± 1.4 days.
The mean duration until attainment of a symptom-free status was 6.5 ± 2.7 days. A total of 49.1% of patients were symptom-free after 5 days, 77.6% after 7 days, 93.5% after 10 days, and 98.3% after 20 days (Figure 2). Only 1.4% of observed patients (n = 36) were reported not to attain symptom-free status during the observational period.
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Figure 2.
Cumulative increase in proportion of symptom-free patients during moxifloxacin treatment.
Treatment-emergent adverse events (TEAEs) were reported in 2.13% (n = 57) patients during the observational period. The most common TEAEs included diarrhea (0.52%, n = 14 patients), nausea (0.41%, n = 11), dizziness (0.30%, n = 8), dyspepsia (0.22%, n = 6), fatigue (0.15%, n = 4), and headache (0.15%, n = 4). TEAEs considered potentially drug related were reported in 1.91% (n = 51) patients. Moxifloxacin treatment was interrupted in eight of these patients, withdrawn in four, and the dose was reduced in one patient. By the end of the observational period, drug-related TEAEs had resolved in 40 of the 51 patients, resolved with sequelae in another three, and improved in eight patients.
Four patients (0.15%) experienced 11 serious TEAEs (n = 2, atrial fibrillation; n = 1 each of: acute myocardial infarction, cardiac flutter, diplopia, vomiting, allergic edema, amnesia, dizziness, dyspnea, and skin reaction). The serious TEAEs were considered to be drug related. All serious TEAEs had resolved by the end of the observational period, following interruption of moxifloxacin treatment in three patients and treatment withdrawal in one patient.
None of the 10 patients who received moxifloxacin at above the recommended dose of 400 mg once daily (n = 5, 600 mg/day; n = 5, 800 mg/day) experienced an adverse event.
The efficacy of moxifloxacin was rated by physicians as 'very good' or 'good' in 97.7% of patients, 'sufficient' in 1.8%, and 'insufficient' in 0.5%. Physicians' assessments of the efficacy of moxifloxacin in patient subgroups categorized by gender, age, and Anthonisen grade are presented in Table 5. The tolerability of moxifloxacin was rated by physicians as 'very good' or 'good' in 97.8% of patients, 'sufficient' in 1.8%, and 'insufficient' in 0.3%.
Approximately 99% of both physicians and patients stated that they were 'very satisfied' or 'satisfied' with the therapeutic effect of moxifloxacin. Compared with the antibiotic treatment during the previous episode of AECB, physicians rated moxifloxacin as better in 77.5% of patients, equal in 5.3%, and worse in 0.2%, with missing data in 17.0%. Moxifloxacin was considered to have an earlier onset of action compared with the previous antibiotic in 73.5% of patients, equivalent onset in 9.5%, and later onset in 1.3%, with missing data in 15.7%. Physicians reported that they would prescribe moxifloxacin again in 98.1% of patients.
Results
Patient Population
A total of 2672 patients were enrolled in the study and included in the safety population. The efficacy population consisted of 2536 patients, after exclusion of 136 (5.1%) patients from the safety population, most commonly because of age < 35 years (n = 119) (Figure 1).
(Enlarge Image)
Figure 1.
Patient disposition.
Demographic and disease characteristics of the efficacy population at baseline are presented in Table 1. Patient ages ranged from 35 to 94 years, with approximately one-third of patients (31.6%) aged above 65 years. Over one-half of patients (53.9%) were past or current smokers. Over the past 12 months, patients had experienced a mean of 2.7 ± 1.9 (range 1.0–20.0) episodes of AECB. An antibiotic was prescribed for the previous episode of AECB in 62.2% of patients, most commonly amoxicillin (13.6% of patients), usually combined with clavulanic acid.
The most common symptoms in the current AECB episode were increased sputum purulence, worsening of dyspnea, and increased sputum volume (Table 1); 42.9% of patients were classified as Anthonisen type I, 40.2% as type II, and 16.2% as type III, with data missing in the remainder (Table 1). One-half of patients (49.9%) complained of an infection of the upper respiratory tract in the past 5 days. An impact on daily life activities was reported by 90.4%, over a mean duration of 6.6 ± 5.5 days. Sleep disturbances were reported by 68.6% of patients, with impact on a mean of 4.1 ± 3.7 nights. The impact of the current AECB episode on daily activities and sleep disturbance in patient subgroups categorized by gender, age, smoking status, concomitant diseases, Anthonisen grade, and number of severe symptoms is presented in Table 2. Mean FEV1 (measured in 1261 patients) was 2.0 ± 0.9 liters. Patients experienced AECB symptoms for a mean of 7.0 ± 5.0 days before initiation of treatment with moxifloxacin.
Concomitant diseases of special interest recorded by investigators included COPD (66.0% of patients), emphysema (23.8%), asthma (16.6%), cardiac ischemia (23.1%), cor pulmonale (10.6%), and diabetes (10.1%). Concomitant medications were taken by 93.3% of patients, most commonly a corticosteroid (32.8% overall, including 40.8% of Anthonisen type I, 28.0% of type II, and 24.2% of type III patients); the mucolytic ambroxol (18.8%); and the mucolytic/antioxidant, acetylcysteine (18.6%). As expected, a large proportion of patients (83.4%) received comedications to treat their respiratory symptoms.
The most frequently used non-AECB-related comedications were for the treatment of cardiovascular symptoms (36.1% of patients), dermatological diseases (23.0%), dysfunction of the alimentary tract and metabolism (22.2%), and ophthalmological diseases (20.5%).
Moxifloxacin Treatment
Moxifloxacin was administered at the recommended dose of 400 mg once daily in 99.6% (n = 2526) of enrolled patients, with a higher dose of 600 mg/day (n = 5) or 800 mg/day (n = 5) in the remainder.
The mean (SD) duration of moxifloxacin treatment was 6.4 ± 1.9 days (range: 1.0–15.0 days) in the efficacy population; 55.2% of patients were treated for 5 days, 29.1% for 7 days, and 14.0% for 10 days. Mean durations of treatment in patients with Anthonisen type I, type II, and type III AECB were 6.4 ± 1.9, 6.4 ± 1.9, and 6.2 ± 1.8 days, respectively, and were 6.3 ± 1.9 days in never smokers versus 6.5 ± 1.9 days in past or current smokers. Durations of treatment were 6.0 ± 1.8 days for patients aged < 50 years, 6.4 ± 1.9 for age ≥ 50 to < 65, 6.7 ± 2.0 days for age ≥ 65 to < 80, and 7.0 ± 1.9 days for age ≥ 80 years.
The last follow-up visit was performed after a mean of 9.8 ± 6.2 days (range 2–66 days) from the initiation of moxifloxacin treatment. Moxifloxacin was discontinued prematurely in 23 (0.9%) patients, because of the patient's decision (n = 4), insufficient efficacy (n = 3), adverse events (n = 9), and 'other reasons' (n = 8) (multiple responses included).
Efficacy Assessments of Moxifloxacin Treatment
An improvement or relief of the symptoms of AECB that were present at baseline was reported in 89.4% of patients for sputum volume, 97.2% for fever, 86.0% for cough, 87.7% for dyspnea, and 77.2% for sputum character during moxifloxacin treatment. Additional symptom changes are presented in Table 3.
Improvement in symptoms occurred after a mean of 3.4 ± 1.4 days of moxifloxacin treatment. Improvements occurred by 3 days in 60.7% of patients, 5 days in 93.2%, and 10 days in 99.3%. Only 0.6% of patients (n = 14) experienced no symptom improvements during the observational period.
The mean duration of treatment until symptom improvement in patients with Anthonisen type I, II, and III AECB was 3.6 ± 1.5, 3.3 ± 1.4, and 3.4 ± 1.4 days, respectively (Table 4), 3.4 ± 1.4 days in never smokers versus 3.5 ± 1.5 days in past or current smokers, 3.6 ± 1.6 days in concomitant corticosteroid users versus 3.4 ± 1.3 in non-corticosteroid users, and 3.7 ± 1.5 days in patients with >3 exacerbations versus 3.4 ± 1.4 days in patients with ≤3 exacerbations in the previous 12 months. Duration of treatment until symptom improvement was 3.2 ± 1.4 days in patients aged < 50 years, 3.4 ± 1.4 days for age ≥ 50 to < 65, 3.6 ± 1.5 days for age ≥ 65 to < 80, and 3.7 ± 1.9 for age ≥ 80 years. Mean duration of treatment until symptom improvement in patients with concomitant diseases is described in Table 4. For patients with COPD (diagnosed by the attending physician), the mean duration of moxifloxacin treatment until improvement was 3.5 ± 1.4 days.
The mean duration until attainment of a symptom-free status was 6.5 ± 2.7 days. A total of 49.1% of patients were symptom-free after 5 days, 77.6% after 7 days, 93.5% after 10 days, and 98.3% after 20 days (Figure 2). Only 1.4% of observed patients (n = 36) were reported not to attain symptom-free status during the observational period.
(Enlarge Image)
Figure 2.
Cumulative increase in proportion of symptom-free patients during moxifloxacin treatment.
Safety Assessments
Treatment-emergent adverse events (TEAEs) were reported in 2.13% (n = 57) patients during the observational period. The most common TEAEs included diarrhea (0.52%, n = 14 patients), nausea (0.41%, n = 11), dizziness (0.30%, n = 8), dyspepsia (0.22%, n = 6), fatigue (0.15%, n = 4), and headache (0.15%, n = 4). TEAEs considered potentially drug related were reported in 1.91% (n = 51) patients. Moxifloxacin treatment was interrupted in eight of these patients, withdrawn in four, and the dose was reduced in one patient. By the end of the observational period, drug-related TEAEs had resolved in 40 of the 51 patients, resolved with sequelae in another three, and improved in eight patients.
Four patients (0.15%) experienced 11 serious TEAEs (n = 2, atrial fibrillation; n = 1 each of: acute myocardial infarction, cardiac flutter, diplopia, vomiting, allergic edema, amnesia, dizziness, dyspnea, and skin reaction). The serious TEAEs were considered to be drug related. All serious TEAEs had resolved by the end of the observational period, following interruption of moxifloxacin treatment in three patients and treatment withdrawal in one patient.
None of the 10 patients who received moxifloxacin at above the recommended dose of 400 mg once daily (n = 5, 600 mg/day; n = 5, 800 mg/day) experienced an adverse event.
Summary Assessments of Moxifloxacin Treatment
The efficacy of moxifloxacin was rated by physicians as 'very good' or 'good' in 97.7% of patients, 'sufficient' in 1.8%, and 'insufficient' in 0.5%. Physicians' assessments of the efficacy of moxifloxacin in patient subgroups categorized by gender, age, and Anthonisen grade are presented in Table 5. The tolerability of moxifloxacin was rated by physicians as 'very good' or 'good' in 97.8% of patients, 'sufficient' in 1.8%, and 'insufficient' in 0.3%.
Approximately 99% of both physicians and patients stated that they were 'very satisfied' or 'satisfied' with the therapeutic effect of moxifloxacin. Compared with the antibiotic treatment during the previous episode of AECB, physicians rated moxifloxacin as better in 77.5% of patients, equal in 5.3%, and worse in 0.2%, with missing data in 17.0%. Moxifloxacin was considered to have an earlier onset of action compared with the previous antibiotic in 73.5% of patients, equivalent onset in 9.5%, and later onset in 1.3%, with missing data in 15.7%. Physicians reported that they would prescribe moxifloxacin again in 98.1% of patients.