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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00656747




Registration number
NCT00656747
Ethics application status
Date submitted
4/04/2008
Date registered
11/04/2008
Date last updated
1/12/2014

Titles & IDs
Public title
Moxifloxacin Versus Amoxicillin Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis
Scientific title
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.
Secondary ID [1] 0 0
2007-006096-37
Secondary ID [2] 0 0
11980
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Bronchitis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Infection 0 0 0 0
Other infectious diseases
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelox (Moxifloxacin, BAY12-8039)
Treatment: Drugs - Amoxicillin clavulanic acid

Active comparator: Arm 2 -

Experimental: Arm 1 -


Treatment: Drugs: Avelox (Moxifloxacin, BAY12-8039)
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.

Treatment: Drugs: Amoxicillin clavulanic acid
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical failure at 8 weeks post therapy
Timepoint [1] 0 0
At day 63
Secondary outcome [1] 0 0
Clinical failure rates
Timepoint [1] 0 0
Through to day 35
Secondary outcome [2] 0 0
Bacteriological eradication rates
Timepoint [2] 0 0
Through to day 63
Secondary outcome [3] 0 0
Clinical failure rates for subjects with positive sputum culture at enrollment
Timepoint [3] 0 0
Through to day 63
Secondary outcome [4] 0 0
Weekly mean symptom scores measured by the AECB SS
Timepoint [4] 0 0
Through to day 63
Secondary outcome [5] 0 0
Rates and speed of symptom relief measured by the AECB SS
Timepoint [5] 0 0
Through to day 63
Secondary outcome [6] 0 0
Clinical failure rates for subjects with co-administration of systemic corticosteroids (stratum 1)
Timepoint [6] 0 0
Through to day 63
Secondary outcome [7] 0 0
Clinical failure rates for subjects without co-administration of systemic corticosteroids (stratum 2)
Timepoint [7] 0 0
Through to day 63
Secondary outcome [8] 0 0
Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators
Timepoint [8] 0 0
Through to day 63
Secondary outcome [9] 0 0
Improvement in symptoms burden measured by the AECB SS
Timepoint [9] 0 0
Through to day 63
Secondary outcome [10] 0 0
Improvement in health related QoL measured by the SGRQ
Timepoint [10] 0 0
Through to day 63
Secondary outcome [11] 0 0
spirometry tests will be compared between treatment groups
Timepoint [11] 0 0
Through to day 63
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Through to day 63
Secondary outcome [13] 0 0
Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea
Timepoint [13] 0 0
Through to day 63

Eligibility
Key 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
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2010
Sample size
Target
Accrual to date
Final
1372
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
- Concord
Recruitment hospital [2] 0 0
- Brisbane
Recruitment hospital [3] 0 0
- Adelaide
Recruitment hospital [4] 0 0
- Woodville
Recruitment hospital [5] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
5041 - Adelaide
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Andorra
State/province [1] 0 0
Escaldes - Engordany
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
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Argentina
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Ciudad Auton. de Buenos Aires
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Argentina
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Tucuman
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Argentina
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Vicente López
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Belgium
State/province [6] 0 0
Aalst
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Belgium
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Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles - Brussel
Country [9] 0 0
Belgium
State/province [9] 0 0
Halen
Country [10] 0 0
Belgium
State/province [10] 0 0
Lommel
Country [11] 0 0
Belgium
State/province [11] 0 0
Moerkerke
Country [12] 0 0
Belgium
State/province [12] 0 0
Namur
Country [13] 0 0
Belgium
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Yvoir
Country [14] 0 0
Brazil
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Minas Gerais
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Brazil
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Rio Grande do Sul
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Brazil
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Sao Paulo
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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New Brunswick
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Nova Scotia
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Ontario
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Quebec
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Chile
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Santiago
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Chile
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Valparaíso
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Chile
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Viña del Mar
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China
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Guangdong
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China
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Hunan
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China
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Liaoning
Country [30] 0 0
China
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Sichuan
Country [31] 0 0
China
State/province [31] 0 0
Beijing
Country [32] 0 0
China
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Shanghai
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China
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Tianjin
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Colombia
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Cauca
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Colombia
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Bogotá
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Bucaramanga
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Zagreb
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Lovosice
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Marseille
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Mont-de-marsan
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Nice
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Perpignan
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Baden-Württemberg
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Bayern
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Germany
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen
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Eastern Cape
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South Africa
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Freestate
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South Africa
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Gauteng
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South Africa
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KwaZulu Natal
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South Africa
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Limpopo
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South Africa
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Mpumalanga
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South Africa
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Western Cape
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Spain
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Barcelona
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Spain
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Illes Baleares
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Spain
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Valencia
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Spain
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Guadalajara
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Spain
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Madrid
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Switzerland
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Aargau
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Switzerland
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Basel-Landschaft
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Switzerland
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Basel-Stadt
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Basel
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Bern
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Thun
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Switzerland
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Wettingen
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Switzerland
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Zürich
Country [139] 0 0
Thailand
State/province [139] 0 0
Bangkok
Country [140] 0 0
Thailand
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Chiang Mai
Country [141] 0 0
Thailand
State/province [141] 0 0
Nonthaburi
Country [142] 0 0
United Kingdom
State/province [142] 0 0
Stratchclyde
Country [143] 0 0
United Kingdom
State/province [143] 0 0
Warwickshire

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00656747
Trial related presentations / publications
Wilson R, Anzueto A, Miravitlles M, Arvis P, Farago G, Haverstock D, Trajanovic M, Sethi S. A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology. Int J Chron Obstruct Pulmon Dis. 2011;6:373-83. doi: 10.2147/COPD.S21071. Epub 2011 Jun 29.
Wilson R, Anzueto A, Miravitlles M, Arvis P, Haverstock D, Trajanovic M, Sethi S. Prognostic factors for clinical failure of exacerbations in elderly outpatients with moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis. 2015 Jun 2;10:985-93. doi: 10.2147/COPD.S80926. eCollection 2015.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00656747