Moxifloxacin versus amoxicillin/clavulanic acid in outpatient acute exacerbations of COPD: MAESTRAL results

Abstract

Bacterial infections causing acute exacerbations of chronic obstructive pulmonary disease (AECOPD) frequently require antibacterial treatment. More evidence is needed to guide antibiotic choice. The Moxifloxacin in Acute Exacerbations of Chronic Bronchitis TriaL (MAESTRAL) was a multiregional, randomised, double-blind non-inferiority outpatient study. Patients were aged ≥ 60 yrs, with an Anthonisen type I exacerbation, a forced expiratory volume in 1 s < 60% predicted and two or more exacerbations in the last year. Following stratification by steroid use patients received moxifloxacin 400 mg p.o. q.d. (5 days) or amoxicillin/clavulanic acid 875/125 mg p.o. b.i.d. (7 days). The primary end-point was clinical failure 8 weeks post-therapy in the per protocol population. Moxifloxacin was noninferior to amoxicillin/clavulanic acid at the primary end-point (111 (20.6%) out of 538, versus 114 (22.0%) out of 518, respectively; 95% CI -5.89-3.83%). In patients with confirmed bacterial AECOPD, moxifloxacin led to significantly lower clinical failure rates than amoxicillin/clavulanic acid (in the intent-to-treat with pathogens, 62 (19.0%) out of 327 versus 85 (25.4%) out of 335, respectively; p=0.016). Confirmed bacterial eradication at end of therapy was associated with higher clinical cure rates at 8 weeks post-therapy overall (p=0.0014) and for moxifloxacin (p=0.003). Patients treated with oral corticosteroids had more severe disease and higher failure rates. The MAESTRAL study showed that moxifloxacin was as effective as amoxicillin/clavulanic acid in the treatment of outpatients with AECOPD. Both therapies were well tolerated.

Figure 1–

Definitions for the populations involved in the study. Patients could be excluded for more than one reason. Intent-to-treat (ITT)/safety population, these randomised patients received at least one dose of the study drug and had one observation after initiation of the study treatment. ITT with pathogens population: patients valid for ITT with a minimum of one pre-therapy potentially pathogenic bacterium. Per protocol (PP) population (primary anaylsis population), patients with an acute exacerbation at enrolment who received the study drug for a minimum of 48 h (cases of clinical failure) or received ≥80% of the study medication (cases of clinical cure). All PP population had data for clinical evaluation at 8 weeks post-therapy (except for clinical failures prior to the 8-week post-therapy visit) and had no protocol violations. PP with pathogens population: these patients were drawn from the PP population and had a minimum of one potentially pathogenic bacterium cultured from the sputum they provided prior to start of therapy and where a bacteriological evaluation was available during the study. GCP: Good Clinical Practice; ^#: data taken from one site (n=9 patients in total) judged to be unreliable and excluded from analysis; ^¶: the majority of patients with essential data missing or invalid were either lost to follow-up or consent was withdrawn (58 and 56% for moxifloxacin and amoxicillin/clavulanic acid, respectively).

Figure 2–

Kaplan–Meier curves of time to clinical failure/relapse.

Figure 3–

Clinical failure rates at 8 weeks post-therapy. PP: per protocol; ITT: intent-to-treat.