Moxifloxacin in Acute Exacerbations of Chronic Bronchitis
Moxifloxacin in Acute Exacerbations of Chronic Bronchitis
The AVANTI study (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, multicenter, observational study conducted at 182 investigational centers in 8 countries (Albania, Bosnia and Herzegovina, Kazakhstan, Macedonia, Moldova, Russian Federation, Slovakia, and Ukraine) between 8 April 2008 and 6 April 2010.
The observational period for each patient commenced at the initiation of treatment with moxifloxacin (Avelox®) for AECB and was continued until an improvement or relief of symptoms at follow-up visit or premature discontinuation. Up to two follow-up visits were planned, with the last assessment following the final intake of moxifloxacin.
Male or female outpatients aged ≥ 35 years with a diagnosis of AECB were included in the study. The diagnosis of AECB and of any concomitant diseases was provided by attending physicians, who were pulmonologists or internal medicine specialists (approximately 60%), general practitioners (10%), or practitioners from other specialties. An exacerbation of chronic bronchitis was considered to be present when the patient experienced an acute increase in respiratory symptoms, including dyspnea, sputum volume, and/or sputum clearance. Exacerbations were classified into Anthonisen types I, II, or III. Exclusion criteria were limited to contraindications to the use of moxifloxacin, as described in the locally available Summary of Product Characteristics.
Data on disease characteristics, risk factors, and the impact of exacerbations on daily life were collected from patients before initiation of moxifloxacin treatment.
The study protocol was approved by the local independent ethics committee or institutional review board, as applicable, at each of the investigator sites. At the national level, the study was approved in Albania by the Bioethics National Committee of the Ministry of Health, in Moldova by the National Ethical Committee, in the Russian Republic by the Ethical Committee at the Federal Service on Surveillance in Healthcare and Social Development, in Slovakia by the Ethical Committee of the Bratislava Region, and in Ukraine by the Central Ethics Commission of the Ministry of Health. Notification on the study protocol, following regulatory requirements for non-interventional studies, was provided in Bosnia and Herzegovina to the Ministry of Health, and in Kazakhstan to the local regulatory authority and the National Center for Drug Expertise, Medical Devices and Medical Equipment. In Macedonia, no ethics committee approval or notification was requested at national level. All patients provided informed consent in accordance with local regulations.
Moxifloxacin was prescribed according to the medical judgment of the investigator and in accordance with the guidelines from the European Medicines Agency, the US Food and Drug Administration, and local regulations (e.g. Avelox® (moxifloxacin hydrochloride) US prescribing information).
The dose of moxifloxacin recommended for the treatment of AECB in the study was 400 mg once daily, consistent with the local Summary of Product Characteristics. Final decisions on the dose of moxifloxacin and on the use of concomitant medications were at the discretion of the attending physician.
Efficacy assessments for each patient included the frequency of improvement of different symptoms (including sputum volume, sputum character, fever, cough, and dyspnea), the frequency of cure (i.e. symptom-free status), the time to improvement in symptoms and to cure, and general assessments of the effectiveness of moxifloxacin treatment using methodologies similar to those employed in the GIANT study.
Safety evaluations included adverse events reported during the study, coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 13.0, and a general subjective tolerability assessment by investigators.
Physicians additionally provided summary assessments of the overall efficacy and tolerability of moxifloxacin into the categories: 'very good', 'good', 'sufficient', and 'insufficient'. Both physicians and patients provided an assessment of their satisfaction with the therapeutic effect of moxifloxacin. Finally, for patients with available data, physicians compared the overall effect and onset of action of moxifloxacin against the antibiotic used to treat the previous episode of AECB.
Efficacy and safety outcomes were analyzed by descriptive statistics. As appropriate for non-interventional studies, statistical tests were not performed. The safety population included all patients who took at least one dose of study medication and provided information on adverse events. The efficacy population included all patients who took at least one dose of study medication and provided information on the efficacy of treatment.
A minimum of 1600 patients were planned to be included in the study. As 2672 patients were actually included, adverse events occurring at a frequency of 0.125% (1:800 patients) could be detected with a probability of 95%.
Methods
Study Design
The AVANTI study (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, multicenter, observational study conducted at 182 investigational centers in 8 countries (Albania, Bosnia and Herzegovina, Kazakhstan, Macedonia, Moldova, Russian Federation, Slovakia, and Ukraine) between 8 April 2008 and 6 April 2010.
The observational period for each patient commenced at the initiation of treatment with moxifloxacin (Avelox®) for AECB and was continued until an improvement or relief of symptoms at follow-up visit or premature discontinuation. Up to two follow-up visits were planned, with the last assessment following the final intake of moxifloxacin.
Patients
Male or female outpatients aged ≥ 35 years with a diagnosis of AECB were included in the study. The diagnosis of AECB and of any concomitant diseases was provided by attending physicians, who were pulmonologists or internal medicine specialists (approximately 60%), general practitioners (10%), or practitioners from other specialties. An exacerbation of chronic bronchitis was considered to be present when the patient experienced an acute increase in respiratory symptoms, including dyspnea, sputum volume, and/or sputum clearance. Exacerbations were classified into Anthonisen types I, II, or III. Exclusion criteria were limited to contraindications to the use of moxifloxacin, as described in the locally available Summary of Product Characteristics.
Data on disease characteristics, risk factors, and the impact of exacerbations on daily life were collected from patients before initiation of moxifloxacin treatment.
The study protocol was approved by the local independent ethics committee or institutional review board, as applicable, at each of the investigator sites. At the national level, the study was approved in Albania by the Bioethics National Committee of the Ministry of Health, in Moldova by the National Ethical Committee, in the Russian Republic by the Ethical Committee at the Federal Service on Surveillance in Healthcare and Social Development, in Slovakia by the Ethical Committee of the Bratislava Region, and in Ukraine by the Central Ethics Commission of the Ministry of Health. Notification on the study protocol, following regulatory requirements for non-interventional studies, was provided in Bosnia and Herzegovina to the Ministry of Health, and in Kazakhstan to the local regulatory authority and the National Center for Drug Expertise, Medical Devices and Medical Equipment. In Macedonia, no ethics committee approval or notification was requested at national level. All patients provided informed consent in accordance with local regulations.
Study Medication
Moxifloxacin was prescribed according to the medical judgment of the investigator and in accordance with the guidelines from the European Medicines Agency, the US Food and Drug Administration, and local regulations (e.g. Avelox® (moxifloxacin hydrochloride) US prescribing information).
The dose of moxifloxacin recommended for the treatment of AECB in the study was 400 mg once daily, consistent with the local Summary of Product Characteristics. Final decisions on the dose of moxifloxacin and on the use of concomitant medications were at the discretion of the attending physician.
Efficacy and Safety Assessments
Efficacy assessments for each patient included the frequency of improvement of different symptoms (including sputum volume, sputum character, fever, cough, and dyspnea), the frequency of cure (i.e. symptom-free status), the time to improvement in symptoms and to cure, and general assessments of the effectiveness of moxifloxacin treatment using methodologies similar to those employed in the GIANT study.
Safety evaluations included adverse events reported during the study, coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 13.0, and a general subjective tolerability assessment by investigators.
Physicians additionally provided summary assessments of the overall efficacy and tolerability of moxifloxacin into the categories: 'very good', 'good', 'sufficient', and 'insufficient'. Both physicians and patients provided an assessment of their satisfaction with the therapeutic effect of moxifloxacin. Finally, for patients with available data, physicians compared the overall effect and onset of action of moxifloxacin against the antibiotic used to treat the previous episode of AECB.
Statistical Analyses
Efficacy and safety outcomes were analyzed by descriptive statistics. As appropriate for non-interventional studies, statistical tests were not performed. The safety population included all patients who took at least one dose of study medication and provided information on adverse events. The efficacy population included all patients who took at least one dose of study medication and provided information on the efficacy of treatment.
A minimum of 1600 patients were planned to be included in the study. As 2672 patients were actually included, adverse events occurring at a frequency of 0.125% (1:800 patients) could be detected with a probability of 95%.
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