By Sandra Ripley Distelhorst
SEATTLE, Wash -- November 12, 2008 -- While moxifloxacin therapy did not achieve a statistically superior cure rate compared with placebo in patients with acute bacterial sinusitis (ABS), patients treated with the drug had significantly greater improvements in health outcomes and used fewer concomitant medicines, according to a study presented here at the American College of Allergy, Asthma & Immunology (ACAAI) annual conference.
Results from the phase 3, prospective, multicentre, placebo-controlled, randomised, double-blind clinical study were presented in a poster session on November 10.
Moxifloxacin is approved for the treatment of ABS in a 7-day or 10-day course of therapy. Reducing treatment duration can have a number of benefits, including enhanced patient compliance, reduced potential for adverse effects, and decreased risk of developing antimicrobial resistance.
James A. Hadley, MD, University of Rochester Medical School, Rochester, New York, and colleagues designed the study in consultation with the Food and Drug Administration. They included patients aged 18 years or older with a clinical diagnosis of ABS as well as signs and symptoms (as defined by radiographic and clinical criteria) present for 7 to 28 days.
Bacteriology was confirmed by sinus tap at baseline. Patients were randomised in a 2:1 design to receive 5 days of oral moxifloxacin 400 mg QD (n = 251) or placebo (n = 123). Symptom relief medication was permitted.
The primary study endpoint was clinical response at test-of-cure (TOC) 1 to 3 days after the end of therapy in the modified intent-to-treat population, which included patients with positive culture for 1 of 5 prespecified pathogens. This cohort included 73 patients in the treatment group and 45 in the placebo group.
Time to symptom relief was based on the Sinonasal Outcome Test-16 (SNOT-16). After day 3, moxifloxacin-treated patients experienced faster symptom resolution than placebo-treated patients (78.1% vs 66.7%; P = .189). Clinical failure rates were 19.2% for the treatment group and 33.3% for the placebo group (P = .122).
Significantly fewer patients discontinued treatment due to lack of therapeutic effect in the treatment group compared with placebo (8.2 vs 22.2, P = .031). Serious adverse events occurred in 0.4% of patients in the treatment group and 0.8% of placebo patients, and no adverse events were considered to be drug-related.
Dr. Hadley noted that while clinical cure rates were numerically higher in moxifloxacin-treated patients compared with placebo, the difference did not reach statistical significance.
Moxifloxacin-treated patients experienced benefits over placebo with significantly lower rates of discontinuation due to therapeutic insufficiency and faster symptom relief after 3 days of treatment.
There was a greater than expected response rate in the placebo arm, Dr. Hadley noted, and he cautioned that as the enrolment criteria stated symptom duration of 7 to 28 days, patients may have been recovering spontaneously before the start of treatment.
While the current study is one of the most rigorous ABS clinical trials, owing to its placebo-controlled design and microbiological sampling, further study in this area is warranted, the authors stated.
Funding for this study was provided by Bayer HealthCare.
[Presentation title: Efficacy and Safety of Moxifloxacin 5-Day Therapy vs Placebo in Acute Bacterial Sinusitis. Abstract 64]
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