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

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.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Bronchitis
• Intervention / Treatment: Drug: Amoxicillin clavulanic acid; Drug: Avelox (Moxifloxacin, BAY12-8039)

• Study Type: Interventional
• Enrollment (Actual): 1372
• Phase: Phase 4

Contacts and Locations

Study Locations

• Andorra
  • Escaldes - Engordany, Andorra
• Argentina
  • Vicente López, Argentina, 1638
  • Buenos Aires
    • Florencio Varela, Buenos Aires, Argentina
    • Quilmes, Buenos Aires, Argentina
  • Ciudad Auton. de Buenos Aires
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1425AWC
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, 1426
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1424BSF
    • Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina
  • Tucuman
    • San Miguel de Tucumán, Tucuman, Argentina, 4000
    • San Miguel de Tucumán, Tucuman, Argentina
• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
  • Queensland
    • Brisbane, Queensland, Australia, 4101
  • South Australia
    • Adelaide, South Australia, Australia, 5041
    • Woodville, South Australia, Australia, 5011
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
• Belgium
  • Aalst, Belgium, 9300
  • Antwerpen, Belgium, 2018
  • Bruxelles - Brussel, Belgium, 1020
  • Halen, Belgium, 3545
  • Lommel, Belgium, 3920
  • Moerkerke, Belgium, 8340
  • Namur, Belgium, 5000
  • Yvoir, Belgium, 5530
• Brazil
  • Minas Gerais
    • Juiz de Fora, Minas Gerais, Brazil, 36036-110
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 04032-060
    • São Paulo, Sao Paulo, Brazil, 05403-900
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
    • Edmonton, Alberta, Canada, T6G 2B7
    • Edmonton, Alberta, Canada, T6L 5X8
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 8E7
    • Vancouver, British Columbia, Canada, V5Z 4E1
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
    • Winnipeg, Manitoba, Canada, R3A 1R8
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2K 2T8
    • Saint John, New Brunswick, Canada, E2M 3W5
  • Nova Scotia
    • Antigonish, Nova Scotia, Canada, B2G 2C2
    • Sydney Mines, Nova Scotia, Canada, B1V 2Y5
  • Ontario
    • Burlington, Ontario, Canada, L7R 3X4
    • Hamilton, Ontario, Canada, L8N 4A6
    • London, Ontario, Canada, N6A 4V2
    • London, Ontario, Canada, N6A 5G6
    • Toronto, Ontario, Canada, M6H 3M2
  • Quebec
    • Longueuil, Quebec, Canada, J4N 1E1
    • Montreal, Quebec, Canada, H2L 4M1
    • Sherbrooke, Quebec, Canada, JIH 4J6
• Chile
  • Santiago, Chile
  • Valparaíso, Chile
  • Viña del Mar, Chile
• China
  • Beijing, China, 100050
  • Beijing, China, 100020
  • Shanghai, China, 200233
  • Shanghai, China, 200040
  • Shanghai, China, 200003
  • Tianjin, China, 300052
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
    • Guangzhou, Guangdong, China, 510405
  • Hunan
    • Changsha, Hunan, China, 410013
  • Liaoning
    • Shengyang, Liaoning, China, 110004
    • Shenyang, Liaoning, China, 110001
  • Sichuan
    • Chengdu, Sichuan, China, 610041
• Colombia
  • Bogotá, Colombia
  • Bucaramanga, Colombia
  • Cali, Colombia
  • Medellín, Colombia
  • Santafe de Bogotá, Colombia
  • Cauca
    • Cali, Cauca, Colombia
• Croatia
  • Osijek, Croatia, 310 00
  • Petrinja, Croatia, 44 250
  • Rijeka, Croatia, 510 00
  • Zagreb, Croatia, 10000
• Czech Republic
  • Kyjov, Czech Republic, 697 01
  • Lovosice, Czech Republic, 410 02
  • Neratovice, Czech Republic, 227 11
  • Pardubice - Trnova, Czech Republic, 530 09
  • Praha - Malesice, Czech Republic, 108 00
  • Praha - Troja, Czech Republic, 182 00
• France
  • Marseille, France, 13009
  • Mont-de-marsan, France, 40000
  • Nice, France, 06000
  • Perpignan, France, 66025
• Germany
  • Berlin, Germany, 14059
  • Berlin, Germany, 10969
  • Berlin, Germany, 12203
  • Berlin, Germany, 13597
  • Berlin, Germany, 10717
  • Berlin, Germany, 10365
  • Berlin, Germany, 12043
  • Hamburg, Germany, 20354
  • Hamburg, Germany, 22305
  • Baden-Württemberg
    • Bad Dürrheim, Baden-Württemberg, Germany, 78073
  • Bayern
    • Augsburg, Bayern, Germany, 86150
  • Brandenburg
    • Cottbus, Brandenburg, Germany, 03050
    • Rüdersdorf, Brandenburg, Germany, 15562
    • Zossen, Brandenburg, Germany, 15806
  • Hessen
    • Frankfurt, Hessen, Germany, 60318
    • Frankfurt, Hessen, Germany, 60389
    • Fulda, Hessen, Germany, 36039
  • Mecklenburg-Vorpommern
    • Neubrandenburg, Mecklenburg-Vorpommern, Germany, 17033
  • Nordrhein-Westfalen
    • Lüdenscheid, Nordrhein-Westfalen, Germany, 58515
  • Rheinland-Pfalz
    • Neuwied, Rheinland-Pfalz, Germany, 56564
  • Sachsen
    • Böhlen, Sachsen, Germany, 04564
    • Delitzsch, Sachsen, Germany, 04509
    • Dresden, Sachsen, Germany, 01307
    • Leipzig, Sachsen, Germany, 04207
    • Leipzig, Sachsen, Germany, 04275
    • Leipzig, Sachsen, Germany, 04357
    • Meißen, Sachsen, Germany, 01662
  • Schleswig-Holstein
    • Bad Segeberg, Schleswig-Holstein, Germany, 23795
    • Lübeck, Schleswig-Holstein, Germany, 23552
• Greece
  • Athens, Greece, 11527
  • Ioannina, Greece, 45500
  • Attica
    • Athens, Attica, Greece, 106 76
  • Larissa
    • Mezourlo, Larissa, Greece, 41110
  • Patras
    • Rio, Patras, Greece, 265 04
• Hong Kong
  • HongKong, Hong Kong
  • Kowloon, Hong Kong
• Indonesia
  • Bandung, Indonesia
  • Jakarta, Indonesia, 13230
  • Surabaya, Indonesia
• Ireland
  • Longford, Ireland
  • Kerry
    • Killarney, Kerry, Ireland
  • Wexford
    • Enniscorthy, Wexford, Ireland
    • Gorey, Wexford, Ireland
  • Wicklow
    • Bray, Wicklow, Ireland
• Italy
  • Ascoli Piceno, Italy, 63100
  • Catania, Italy, 95122
  • Chieti, Italy, 66100
  • Milano, Italy, 20157
  • Milano, Italy, 20123
  • Perugia, Italy, 06156
  • Salerno
    • Pregiato di Cava dei Tirreni, Salerno, Italy, 84013
  • Varese
    • Busto Arsizio, Varese, Italy, 21052
  • Verona
    • Bussolengo, Verona, Italy, 37012
• Latvia
  • Kraslava, Latvia, 5601
  • Riga, Latvia, 1009
  • Riga, Latvia, 1011
  • Riga, Latvia, 1050
  • Talsu, Latvia, 3201
  • Valmiera, Latvia, 4201
  • Ventspils, Latvia, LV-3601
• Lithuania
  • Kaunas, Lithuania
  • Kaunas, Lithuania, LT-50425
  • Klaipeda, Lithuania, LT-94231
  • Siauliai, Lithuania, 76231
  • Vilnius, Lithuania, LT-06122
  • Vilnius, Lithuania, LT-07156
• Mexico
  • Chihuahua, Mexico, 31350
  • Zacatecas, Mexico, 98608
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
  • México
    • Huixquilucan, México, Mexico, CP 52763
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64718
    • Monterrey, Nuevo Leon, Mexico, 66480
  • Yucatán
    • Mérida, Yucatán, Mexico, 97001
• Netherlands
  • Heerlen, Netherlands, 6419 PC
  • Hoofddorp, Netherlands, 2134 TM
  • Meppel, Netherlands, 7943 KA
  • Utrecht, Netherlands, 3582 KE
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
• Pakistan
  • Islamabad, Pakistan
  • Karachi, Pakistan, 75500
  • Sindh
    • Karachi, Sindh, Pakistan, 74800
• Peru
  • Callao, Peru, CALLAO 2
  • Lima, Peru
  • Lima, Peru, 33
  • Lima, Peru, Lima 27
  • Lima, Peru, 31
  • Lima, Peru, LIMA 18
• Philippines
  • Manila, Philippines
  • Quezon City, Philippines
• Portugal
  • Coimbra, Portugal, 3000-075
  • Lisboa, Portugal, 1649-035
  • Lisboa, Portugal, 1169-024
  • Porto, Portugal, 4200
  • S. Martinho do Bispo, Portugal, 3041-856
  • Santarém, Portugal, 2005-177
  • Lisboa
    • Torres Vedras, Lisboa, Portugal, 2560-324
  • Porto
    • Matosinhos, Porto, Portugal, 4454-509
    • Vila Nova de Gaia, Porto, Portugal, 4434-502
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6014
  • Freestate
    • Bloemfontein, Freestate, South Africa, 9324
  • Gauteng
    • Benoni, Gauteng, South Africa, 1500
    • Centurion, Gauteng, South Africa, 0140
    • Kempton Park, Gauteng, South Africa, 1610
    • Pretoria, Gauteng, South Africa, 0002
    • Pretoria, Gauteng, South Africa, 0084
    • Pretoria, Gauteng, South Africa
  • KwaZulu Natal
    • Durban, KwaZulu Natal, South Africa, 4091
    • Durban, KwaZulu Natal, South Africa, 4037
  • Limpopo
    • Thabazimbi, Limpopo, South Africa, 0380
  • Mpumalanga
    • Witbank, Mpumalanga, South Africa, 1035
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
    • Paarl, Western Cape, South Africa, 7647
    • Somerset West, Western Cape, South Africa, 7130
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08034
  • Guadalajara, Spain, 19002
  • Madrid, Spain, 28040
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
    • Sant Boi de Llobregat, Barcelona, Spain, 08830
  • Illes Baleares
    • Palma de Mallorca, Illes Baleares, Spain, 07010
  • Valencia
    • Requena, Valencia, Spain, 46340
• Switzerland
  • Basel, Switzerland, 4031
  • Bern, Switzerland, 3004
  • Thun, Switzerland, 3600
  • Wettingen, Switzerland, 5430
  • Zürich, Switzerland, 8091
  • Zürich, Switzerland, 8048
  • Aargau
    • Aarau, Aargau, Switzerland, 5000
  • Basel-Landschaft
    • Laufen, Basel-Landschaft, Switzerland, 4242
    • Oberwil, Basel-Landschaft, Switzerland, 4104
  • Basel-Stadt
    • Binningen, Basel-Stadt, Switzerland, 4102
• Thailand
  • Bangkok, Thailand, 10330
  • Chiang Mai, Thailand, 50200
  • Nonthaburi, Thailand, 11000
• United Kingdom
  • Stratchclyde
    • Glasgow, Stratchclyde, United Kingdom, G45 9AW
    • Glasgow, Stratchclyde, United Kingdom, G3 8YJ
    • Glasgow, Stratchclyde, United Kingdom, G46 8NY
    • Glasgow, Stratchclyde, United Kingdom, G69 7AD
    • Glasgow, Stratchclyde, United Kingdom
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV7 8LA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 2	Drug: 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.
Experimental: Arm 1	Drug: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General 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.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: April 4, 2008
• First Submitted That Met QC Criteria: April 10, 2008
• First Posted (Estimate): April 11, 2008

Study Record Updates

• Last Update Posted (Estimate): December 1, 2014
• Last Update Submitted That Met QC Criteria: November 27, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: lung; smoking; Chronic Obstructive Pulmonary Disease (COPD); lung disease; chronic bronchitis; bronchitis; lungs; Acute exacerbation of COPD (AECOPD); chest infection
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Acute Disease; Bronchitis; Bronchitis, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; beta-Lactamase Inhibitors; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: 11980; 2007-006096-37 (EudraCT Number)