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: MAESTRAL (moxifloxacin in AECB superiority trial)

Phase 4

Completed

Conditions: Acute exacerbation of chronic bronchitis
Acute increase of chronic bronchitis
10004018
10024970

Registration Number: NL-OMON32177

Lead Sponsor: Bayer

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 50

Inclusion Criteria

Study subjects must meet all of the following inclusion criteria:
1. Outpatients
2. Male or female subjects, >=60 years old
3. Subject who can be managed with oral antimicrobials
4. FEV1<=50% predicted at enrollment in addition to a historical record of FEV1 of <=60% within the past 12 months obtained during a stable infection-free period. A historical record of FEV1 is not required if the enrollment FEV1 is less than or equal to 50%.
5. Documented history of 2 or more AECB episodes, within 12 months of study enrollment, requiring a course of systemic antibiotics and/or systemic corticosteroids
6. All symptoms/signs must be present and confirmed by the Investigator:
• Increase in dyspnea
• Purulent sputum
• Increase in sputum volume
7. Subject must provide a purulent sputum sample by deep expectoration prior to randomization for Gram stain, culture and sensitivity testing. The sputum will be assessed macroscopically by the investigator and graded according to the provided color chart.
8. Current or past cigarette smoker with >=20 pack year smoking history (Pack years are calculated by dividing the number of cigarettes smoked per day by 20 (number of cigarettes/pack) and multiplying by the number of years a person has smoked)
9. Subjects must have an infection free interval of at least 30 days prior to enrollment
10. Subjects must be willing and able to complete the questionnaires and subject booklet without assistance
11. Subjects with medical conditions and social status at the time of enrollment compatible with study protocol procedures
12. Willing and able to provide written informed consent

Exclusion Criteria

Subjects who meet at least one of the following exclusion criteria must be excluded from study participation:
1. Known hypersensitivity to quinolones, ß lactams, or to any of the excipients of the study drugs
2. Known to have congenital or acquired QT prolongation
3. Known to have clinically relevant bradycardia
4. Known to have clinically relevant heart failure with reduced left ventricular ejection fraction
5. Known to have previous history of symptomatic arrhythmias
6. Taking QT prolonging drugs, for example class IA or III antiarrhythmic agents (e.g., quinidine, procainamide, amiodarone, sotalol), neuroleptics (e.g., phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, certain antihistaminics (e.g., terfenadine, astemizole, mizolastine), or other QT prolonging drugs (e.g., cisapride, vincamine iv, bepridil, and diphemanil)
7. Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia
8. Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose galactose malabsorption
9. Requiring hemodialysis
10. History of a tendon disease/disorder
11. Known history of liver dysfunction, including known elevated transaminases (ALT and/or AST >3 times the upper limit of normal)
12. Known severe renal impairment with glomerular filtration rate of <30mL/min
13. Known neutropenia (neutrophil count <1000/mm³) caused by immunosuppressive therapy or malignancy
14. Known to have AIDS (CD4 count of <200/mm³), or be HIV positive and receiving Highly Active Anti Retroviral Therapy (HAART) (HIV testing is not mandatory)
15. Known bronchial carcinoma, active pulmonary tuberculosis, known diffuse bronchiectasis, cystic fibrosis, chronic asthma (>15% reversibility), or pneumonia (a chest X ray is not mandatory)
16. Known history of chronic colonization of pathogenic organisms resistant to moxifloxacin and/or amoxicillin clavulanic acid (e.g., Pseudomonas aeruginosa, MRSA)
17. Receiving long term (>4 consecutive weeks) systemic corticosteroid treatment (>10 mg/day of prednisolone or equivalent) (see Section 4.5.7 Prior and Concomitant Medication)
18. Received short course of systemic corticosteroid treatment within 30 days prior to enrollment
19. Requiring intravenous antibiotic therapy for treatment of the current exacerbation
20. Unable to take oral medication
21. Life expectancy of less than 6 months
22. Receiving systemic antibacterial therapy within 30 days prior to study enrollment
23. Requiring concomitant systemic antibacterial agents
24. Use of any investigational drug or device within 30 days of screening, or previously enrolled in this study
25. Requiring home ventilatory support (subjects requiring home/portable oxygen therapy or CPAP for sleep apnea are not excluded) and/or those who have a tracheotomy in situ

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective is to compare the efficacy of moxifloxacin 400 mg PO OD<br /><br>for five days with the respective efficacy of amoxicillin clavulanic acid<br /><br>875/125 mg PO BID for seven days in the treatment of subjects with AECB. The<br /><br>primary efficacy endpoint will be clinical failure rates at 8 weeks post-<br /><br>therapy visit in outpatients with AECB.<br /><br>Clinical failure is defined as the requirement for additional (including<br /><br>increased dose or duration of treatment) systemic antibiotics and/or systemic<br /><br>corticosteroids and/or hospitalization with antibiotic and/or systemic<br /><br>corticosteroid administration within 8 weeks post therapy. </p><br>

Secondary Outcome Measures