Moxifloxacin Versus Amoxicillin Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis

Study Overview
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Brief Summary
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A study to assess the safety and efficacy of moxifloxacin compared to that of amoxicillin-clavulanic acid for the treatment of subjects with acute exacerbation of chronic bronchitis.

Official Title
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MAESTRAL - A Prospective, Multinational, Multicenter, Randomized, Double Blind, Double Dummy, Controlled Study Comparing the Efficacy and Safety of Moxifloxacin to That of Amoxicillin Clavulanic Acid for the Treatment of Subjects With Acute Exacerbations of Chronic Bronchitis.

Conditions
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Chronic Bronchitis

Intervention / Treatment
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* Drug: Avelox (Moxifloxacin, BAY12-8039)
* Drug: Amoxicillin clavulanic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients with chronic bronchitis Male or female subjects, >=60 years old Post bronchodilator forced expiratory volume in one second (FEV1) less than or equal to 60% predicted and FEV1 / forced vital capacity (FVC) less than 70% at enrollment Documented history of 2 or more AECB episodes, within 12 months of study enrollment, requiring a course of systemic antibiotics and/or systemic corticosteroids All symptoms/signs must be present and confirmed by the Investigator: increase in dyspnea purulent sputum increase in sputum volume Current or past cigarette smoker with equal to or greater than 20 pack year smoking history Subjects must be exacerbation free for at least 30 days prior to enrollment Subjects must be willing and able to complete the questionnaires and subject booklet without assistance Exclusion Criteria: Known hypersensitivity to quinolones, ß lactams, or to any of the excipients of the study drugs Known to have congenital or acquired QT prolongation Known to have clinically relevant bradycardia Known to have clinically relevant heart failure with reduced left ventricular ejection fraction Known to have previous history of symptomatic arrhythmias Taking QT prolonging drugs, for example Class Ia or III antiarrhythmic agents or other QT prolonging drugs Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose galactose malabsorption History of a tendon disease/disorder Known history of liver dysfunction (Child-Pugh C), including known elevated transaminase levels (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST] >5 times the upper limit of normal [5 x ULN]) Known severe renal impairment with glomerular filtration rate of <30 mL/min Known neutropenia (neutrophil count <1000/mm3) caused by immunosuppressive therapy or malignancy Known to have Acquired Immunodeficiency Syndrome (AIDS) (CD4 count of <200/mm3), or be human immunodeficiency virus (HIV) positive and receiving highly active anti retroviral therapy (HAART) (testing for HIV is not mandatory) Known chronic asthma (>15% reversibility or at least 200 mL), bronchial carcinoma, active pulmonary tuberculosis, known diffuse bronchiectasis, cystic fibrosis, or pneumonia (a chest x ray is not mandatory) Known history of chronic colonization of pathogenic organisms resistant to moxifloxacin and/or amoxicillin clavulanic acid (eg, P. aeruginosa, methicillin resistant Staphylococcus aureus) Receiving long term (>4 consecutive weeks) systemic corticosteroid treatment (>10 mg/day of prednisolone or equivalent) Received short course of systemic corticosteroid treatment within 30 days prior to enrollment Life expectancy of less than 6 months Receiving systemic antibacterial therapy within 30 days prior to study enrollment Requiring concomitant systemic antibacterial agents Requiring home ventilatory support (subjects requiring home/portable oxygen therapy or continuous positive airway pressure (CPAP) for sleep apnea are not excluded) and/or those who have a tracheotomy in situ History of liver function disorders following previous treatment with amoxicillin-clavulanic acid Receiving disulfiram therapy

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 2<br> | Drug: Amoxicillin clavulanic acid<br>* Subjects will be randomised to amoxicillin-clavulanic acid 875/125 mg PO BID (7 days). Subjects will also take placebo tablets, so that each subject takes 3 tablets per day for 7 days. Prior to randomization, subjects are stratified based on co-administration of short-course systemic steroids.<br>|
| Experimental: Arm 1<br> | Drug: Avelox (Moxifloxacin, BAY12-8039)<br>* Subjects will be randomised to moxifloxacin 400 mg PO OD (5 days). Subjects will also take placebo tablets, so that each subject takes 3 tablets per day for 7 days. Prior to randomization, subjects are stratified based on co-administration of short-course systemic steroids.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical failure at 8 weeks post therapy |  | At day 63 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical failure rates |  | Through to day 35 | 
| Bacteriological eradication rates |  | Through to day 63 | 
| Clinical failure rates for subjects with positive sputum culture at enrollment |  | Through to day 63 | 
| Weekly mean symptom scores measured by the AECB SS |  | Through to day 63 | 
| Rates and speed of symptom relief measured by the AECB SS |  | Through to day 63 | 
| Clinical failure rates for subjects with co-administration of systemic corticosteroids (stratum 1) |  | Through to day 63 | 
| Clinical failure rates for subjects without co-administration of systemic corticosteroids (stratum 2) |  | Through to day 63 | 
| Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators |  | Through to day 63 | 
| Improvement in symptoms burden measured by the AECB SS |  | Through to day 63 | 
| Improvement in health related QoL measured by the SGRQ |  | Through to day 63 | 
| spirometry tests will be compared between treatment groups |  | Through to day 63 | 
| HCRU relat. to chronic bronchitis management incl. rescue med., concomitant med., therap. adjuncts, diagn. procedures, other medical care/medical staff requirement, hospitalizations (incl. ward and duration), and work productivity and activity impairment |  | Through to day 63 | 
| Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea |  | Through to day 63 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease (COPD), Acute exacerbation of COPD (AECOPD), chronic bronchitis, bronchitis, chest infection, smoking, lung disease, lung, lungs