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

Chronic Bronchitis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00656747
• Other study ID #: 11980
• Secondary ID: 2007-006096-37
• Status: Completed
• Phase: Phase 4
• First received: April 4, 2008
• Last updated: November 27, 2014
• Start date: March 2008
• Est. completion date: December 2010

Study information

• Verified date: November 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAndorra: Ethics CommitteeAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaChile: Comisión Nacional de Investigación Científica y TecnológicaChina: Food and Drug AdministrationColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosCroatia: Ministry of HealthCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesGreece: Ministry of Health and WelfareHong Kong: Department of HealthIndonesia: National Agency of Drug and Food ControlIreland: Irish Medicines BoardItaly: Ethics CommitteeLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthMexico: Ministry of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Pakistan: Ministry of HealthPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPhilippines: Bureau of Food and DrugsPortugal: National Pharmacy and Medicines InstituteSouth Africa: Department of HealthSouth Africa: Medicines Control CouncilSpain: Ministry of HealthSpain: Spanish Agency of MedicinesSwitzerland: SwissmedicThailand: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1372
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Disease
• Bronchitis
• Bronchitis, Chronic
• Chronic Bronchitis

Intervention

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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Andorra,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Croatia,  Czech Republic,  France,  Germany,  Greece,  Hong Kong,  Indonesia,  Ireland,  Italy,  Latvia,  Lithuania,  Mexico,  Netherlands,  Pakistan,  Peru,  Philippines,  Portugal,  South Africa,  Spain,  Switzerland,  Thailand,  United Kingdom, 

References & Publications (1)

Wilson R, Anzueto A, Miravitlles M, Arvis P, Faragó 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical failure at 8 weeks post therapy		At day 63	No
Secondary	Clinical failure rates		Through to day 35	No
Secondary	Bacteriological eradication rates		Through to day 63	No
Secondary	Clinical failure rates for subjects with positive sputum culture at enrollment		Through to day 63	No
Secondary	Weekly mean symptom scores measured by the AECB SS		Through to day 63	No
Secondary	Rates and speed of symptom relief measured by the AECB SS		Through to day 63	No
Secondary	Clinical failure rates for subjects with co-administration of systemic corticosteroids (stratum 1)		Through to day 63	No
Secondary	Clinical failure rates for subjects without co-administration of systemic corticosteroids (stratum 2)		Through to day 63	No
Secondary	Need for any change in dosage or additional respiratory medication such as bronchodilators and inhaled steroids, excluding short acting bronchodilators		Through to day 63	No
Secondary	Improvement in symptoms burden measured by the AECB SS		Through to day 63	No
Secondary	Improvement in health related QoL measured by the SGRQ		Through to day 63	No
Secondary	spirometry tests will be compared between treatment groups		Through to day 63	No
Secondary	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	No
Secondary	Safety and tolerability of moxifloxacin versus amoxicillin clavulanic acid, with particular attention to rates of diarrhea		Through to day 63	Yes

External Links

•   Click here and search for drug information provided by the FDA.
•   Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.
•   Click here to find information about studies related to Bayer Healthcare products conducted in Europe
•   Click here to find results for studies related to Bayer Healthcare products.