title: A novel study design for antibiotic trials in acute exacerbations of COPD: MAESTRAL methodology.
abstract: Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747), one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [per os] once daily for 5 days) vs. amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days) in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks after the end of antibiotic therapy, powered for superiority. Patients enrolled are those at high-risk of treatment failure, and all are experiencing an Anthonisen type I exacerbation. Patients are stratified according to oral corticosteroid use to control their effect across antibiotic treatment arms. Secondary endpoints include quality of life, symptom assessments and health care resource use.
authors.affiliation: Host Defence Unit, Royal Brompton Hospital, London, England, UK. r.wilson@rbht.nhs.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.forename: Antonio
authors.initials: A
authors.lastname: Anzueto
authors.forename: Marc
authors.initials: M
authors.lastname: Miravitlles
authors.forename: Pierre
authors.initials: P
authors.lastname: Arvis
authors.forename: Geneviève
authors.initials: G
authors.lastname: Faragó
authors.forename: Daniel
authors.initials: D
authors.lastname: Haverstock
authors.forename: Mila
authors.initials: M
authors.lastname: Trajanovic
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000553:Ambulatory Care; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001372:Aza Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D002170:Canada; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D024841:Fluoroquinolones; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000382:microbiology / Q000503:physiopathology; D000077266:Moxifloxacin; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D011788:Quality of Life; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001993:Bronchodilator Agents; D024841:Fluoroquinolones; D011804:Quinolines; D019980:Amoxicillin-Potassium Clavulanate Combination; D000077266:Moxifloxacin