Clinical trial NCT00656747: Moxifloxacin Versus Amoxicillin Clavulanic Acid in Treatment of Acute Exacerbation of Chronic Bronchitis
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Bronchitis
Keywords: Chronic Obstructive Pulmonary Disease (COPD)
Acute exacerbation of COPD (AECOPD)
chronic bronchitis
bronchitis
chest infection
smoking
lung disease
lung
lungs
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-04-11
Enrollment: 1372
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Clinical failure at 8 weeks post therapy
timeFrame: At day 63
Secondary outcomes:
measure: Clinical failure rates
timeFrame: Through to day 35
measure: Bacteriological eradication rates
timeFrame: Through to day 63
measure: Clinical failure rates for subjects with positive sputum culture at enrollment
timeFrame: Through to day 63
measure: Weekly mean symptom scores measured by the AECB SS
timeFrame: Through to day 63
measure: Rates and speed of symptom relief measured by the AECB SS
timeFrame: Through to day 63
measure: Clinical failure rates for subjects with co-administration of systemic corticosteroids (stratum 1)
timeFrame: Through to day 63
measure: Clinical failure rates for subjects without co-administration of systemic corticosteroids (stratum 2)
timeFrame: Through to day 63
measure: Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators
timeFrame: Through to day 63
measure: Improvement in symptoms burden measured by the AECB SS
timeFrame: Through to day 63
measure: Improvement in health related QoL measured by the SGRQ
timeFrame: Through to day 63
measure: spirometry tests will be compared between treatment groups
timeFrame: Through to day 63
measure: 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
timeFrame: Through to day 63
measure: Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea
timeFrame: Through to day 63
Other outcomes:
Locations:
city: Escaldes - Engordany
country: Andorra
city: Florencio Varela
country: Argentina
state: Buenos Aires
city: Quilmes
country: Argentina
state: Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: San Miguel de Tucumán
country: Argentina
state: Tucuman
city: San Miguel de Tucumán
country: Argentina
state: Tucuman
city: Vicente López
country: Argentina
city: Concord
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Woodville
country: Australia
state: South Australia
city: Nedlands
country: Australia
state: Western Australia
city: Aalst
country: Belgium
city: Antwerpen
country: Belgium
city: Bruxelles - Brussel
country: Belgium
city: Halen
country: Belgium
city: Lommel
country: Belgium
city: Moerkerke
country: Belgium
city: Namur
country: Belgium
city: Yvoir
country: Belgium
city: Juiz de Fora
country: Brazil
state: Minas Gerais
city: Porto Alegre
country: Brazil
state: Rio Grande do Sul
city: São Paulo
country: Brazil
state: Sao Paulo
city: São Paulo
country: Brazil
state: Sao Paulo
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Kelowna
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: Winnipeg
country: Canada
state: Manitoba
city: Saint John
country: Canada
state: New Brunswick
city: Saint John
country: Canada
state: New Brunswick
city: Antigonish
country: Canada
state: Nova Scotia
city: Sydney Mines
country: Canada
state: Nova Scotia
city: Burlington
country: Canada
state: Ontario
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Longueuil
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Santiago
country: Chile
city: Valparaíso
country: Chile
city: Viña del Mar
country: Chile
city: Guangzhou
country: China
state: Guangdong
city: Guangzhou
country: China
state: Guangdong
city: Changsha
country: China
state: Hunan
city: Shengyang
country: China
state: Liaoning
city: Shenyang
country: China
state: Liaoning
city: Chengdu
country: China
state: Sichuan
city: Beijing
country: China
city: Beijing
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Cali
country: Colombia
state: Cauca
city: Bogotá
country: Colombia
city: Bucaramanga
country: Colombia
city: Cali
country: Colombia
city: Medellín
country: Colombia
city: Santafe de Bogotá
country: Colombia
city: Osijek
country: Croatia
city: Petrinja
country: Croatia
city: Rijeka
country: Croatia
city: Zagreb
country: Croatia
city: Kyjov
country: Czech Republic
city: Lovosice
country: Czech Republic
city: Neratovice
country: Czech Republic
city: Pardubice - Trnova
country: Czech Republic
city: Praha - Malesice
country: Czech Republic
city: Praha - Troja
country: Czech Republic
city: Marseille
country: France
city: Mont-de-marsan
country: France
city: Nice
country: France
city: Perpignan
country: France
city: Bad Dürrheim
country: Germany
state: Baden-Württemberg
city: Augsburg
country: Germany
state: Bayern
city: Cottbus
country: Germany
state: Brandenburg
city: Rüdersdorf
country: Germany
state: Brandenburg
city: Zossen
country: Germany
state: Brandenburg
city: Frankfurt
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state: Hessen
city: Frankfurt
country: Germany
state: Hessen
city: Fulda
country: Germany
state: Hessen
city: Neubrandenburg
country: Germany
state: Mecklenburg-Vorpommern
city: Lüdenscheid
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state: Nordrhein-Westfalen
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state: Rheinland-Pfalz
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state: Sachsen
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state: Sachsen
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state: Sachsen
city: Leipzig
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state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Meißen
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state: Sachsen
city: Bad Segeberg
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state: Schleswig-Holstein
city: Lübeck
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state: Schleswig-Holstein
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Athens
country: Greece
state: Attica
city: Mezourlo
country: Greece
state: Larissa
city: Rio
country: Greece
state: Patras
city: Athens
country: Greece
city: Ioannina
country: Greece
city: HongKong
country: Hong Kong
city: Kowloon
country: Hong Kong
city: Bandung
country: Indonesia
city: Jakarta
country: Indonesia
city: Surabaya
country: Indonesia
city: Killarney
country: Ireland
state: Kerry
city: Enniscorthy
country: Ireland
state: Wexford
city: Gorey
country: Ireland
state: Wexford
city: Bray
country: Ireland
state: Wicklow
city: Longford
country: Ireland
city: Pregiato di Cava dei Tirreni
country: Italy
state: Salerno
city: Busto Arsizio
country: Italy
state: Varese
city: Bussolengo
country: Italy
state: Verona
city: Ascoli Piceno
country: Italy
city: Catania
country: Italy
city: Chieti
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Perugia
country: Italy
city: Kraslava
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Riga
country: Latvia
city: Talsu
country: Latvia
city: Valmiera
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city: Ventspils
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city: Kaunas
country: Lithuania
city: Kaunas
country: Lithuania
city: Klaipeda
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city: Siauliai
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city: Vilnius
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city: Vilnius
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city: Guadalajara
country: Mexico
state: Jalisco
city: Huixquilucan
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state: México
city: Monterrey
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state: Nuevo Leon
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Mérida
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state: Yucatán
city: Chihuahua
country: Mexico
city: Zacatecas
country: Mexico
city: Eindhoven
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state: Noord-Brabant
city: Heerlen
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Meppel
country: Netherlands
city: Utrecht
country: Netherlands
city: Karachi
country: Pakistan
state: Sindh
city: Islamabad
country: Pakistan
city: Karachi
country: Pakistan
city: Callao
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city: Lima
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city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Lima
country: Peru
city: Manila
country: Philippines
city: Quezon City
country: Philippines
city: Torres Vedras
country: Portugal
state: Lisboa
city: Matosinhos
country: Portugal
state: Porto
city: Vila Nova de Gaia
country: Portugal
state: Porto
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: S. Martinho do Bispo
country: Portugal
city: Santarém
country: Portugal
city: Port Elizabeth
country: South Africa
state: Eastern Cape
city: Bloemfontein
country: South Africa
state: Freestate
city: Benoni
country: South Africa
state: Gauteng
city: Centurion
country: South Africa
state: Gauteng
city: Kempton Park
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: KwaZulu Natal
city: Durban
country: South Africa
state: KwaZulu Natal
city: Thabazimbi
country: South Africa
state: Limpopo
city: Witbank
country: South Africa
state: Mpumalanga
city: Cape Town
country: South Africa
state: Western Cape
city: Paarl
country: South Africa
state: Western Cape
city: Somerset West
country: South Africa
state: Western Cape
city: Badalona
country: Spain
state: Barcelona
city: Sant Boi de Llobregat
country: Spain
state: Barcelona
city: Palma de Mallorca
country: Spain
state: Illes Baleares
city: Requena
country: Spain
state: Valencia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Guadalajara
country: Spain
city: Madrid
country: Spain
city: Aarau
country: Switzerland
state: Aargau
city: Laufen
country: Switzerland
state: Basel-Landschaft
city: Oberwil
country: Switzerland
state: Basel-Landschaft
city: Binningen
country: Switzerland
state: Basel-Stadt
city: Basel
country: Switzerland
city: Bern
country: Switzerland
city: Thun
country: Switzerland
city: Wettingen
country: Switzerland
city: Zürich
country: Switzerland
city: Zürich
country: Switzerland
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Nonthaburi
country: Thailand
city: Glasgow
country: United Kingdom
state: Stratchclyde
city: Glasgow
country: United Kingdom
state: Stratchclyde
city: Glasgow
country: United Kingdom
state: Stratchclyde
city: Glasgow
country: United Kingdom
state: Stratchclyde
city: Glasgow
country: United Kingdom
state: Stratchclyde
city: Coventry
country: United Kingdom
state: Warwickshire
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.