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) - MAESTRAL

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2007-006096-37-GR
• Date of registration: 02/05/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer HealthCare AG, D-51368 Leverkusen, Germany
• Public title: 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) - MAESTRAL
• Scientific title: 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) - MAESTRAL
• Date of first enrolment: 14/10/2008
• Target sample size: 1786
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006096-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: double - dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Germany, Greece, Ireland, Italy, Latvia, Lithuania, Netherlands, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.Outpatients with chronic bronchitis
2.Male or female subjects, greater than or equal to 60 years old
3.Subject who can be managed with oral antimicrobials
4.Post bronchodilatory FEV1 less than or equal to 60% predicted and FEV1/FVC less than 70% at enrollment.
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 sputum sample. The sputum will be assessed macroscopically by the investigator and should be graded as either yellow, green or rust (according to the provided color chart).
8.Current or past cigarette smoker with great than or equal to 20 pack year smoking history
9.Subjects must be exacerbation-free for 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Known hypersensitivity to quinolones, ß-lactams, or to any of the excipients of the study drugs
2.Pregnant or breast feeding women (women of childbearing potential, based on investigator assessment must have negative urinary pregnancy test)
3.Known to have congenital or acquired QT prolongation
4.Known to have clinically relevant bradycardia
5.Known to have clinically relevant heart failure with reduced left ventricular ejection fraction
6.Known to have previous history of symptomatic arrhythmias
7.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), certain antimicrobials (sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine) or other QT prolonging drugs (e.g., cisapride, vincamine iv, bepridil, and diphemanil)
8.Known electrolyte disturbances that are not controlled, particularly uncorrected hypokalemia
9.Known history of hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
10.History of a tendon disease/disorder
11.Known history of liver dysfunction (Child-Pugh C), including known elevated transaminases (ALT and/or AST greater than 5 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 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)
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)
18.Received short course of systemic corticosteroid treatment within 30 days prior to enrollment
19.Unable to take oral medication
20.Life expectancy of less than 6 months
21.Receiving systemic antibacterial therapy within 30 days prior to study enrollment
22.Requiring concomitant systemic antibacterial agents
23.Use of any investigational drug or device within 30 days of screening, or previously enrolled in this study
24.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
25.History of liver function disorders following previous treatment with amoxicillin-clavulanic acid
26. Receiving disulfiram therapy


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

acute exacerbation of chronic bronchitis
MedDRA version: 9.1 Level: LLT Classification code 10000743 Term: Acute exacerbation of chronic bronchitis

Intervention(s)

Trade Name: Avalox p.o. (film coated tablet)
Product Name: moxifloxacin
Product Code: BAY12-8039
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: moxifloxacin
CAS Number: 186826-86-8
Current Sponsor code: BAY12-8039
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Amoxi-Clavulan STADA 875/125 mg film-coated tablets
Product Name: amoxicillin and clavulanic acid
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: amoxicillin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 875-
INN or Proposed INN: clavulanic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

Primary end point(s): The primary efficacy criterion are clinical failure rates at the follow-up visit 8 weeks after end of treatment. Clinical failure is defined as the requirement for additional or alternate treatment (including increased dose or duration of treatment) for an exacerbation of respiratory symptoms, with systemic antibiotics, and/or systemic corticosteroids, and/or hospitalization with systemic antibiotic and/or systemic corticosteroid administration within 8 weeks post therapy.

Secondary Objective: The secondary objectives will compare the following between the two treatment groups: •Clinical failure rates •Bacteriological eradication rates •Clinical failure rates (for subjects with positive sputum culture at enrollment; for each stratum) •Weekly mean symptom scores measured by the AECB-Symptom Scale (AECB-SS) •Rates and speed of symptom relief measured by the AECB-SS •Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators •Improvement in symptom burden measured by the AECB-SS •Improvement in health-related QoL measured by The St. George’s Hospital Respiratory Questionnaire (SGRQ) •Spirometry tests will be compared between treatment groups at each assessment visit •Healthcare resource utilization/consumption related to chronic bronchitis management •Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea

Secondary ID(s)

2007-006096-37-NL

none

BAY 12-8039/11980