Phase 3 Trial Update of Moxifloxacin for Secondary Peritonitis

SAN DIEGO, CA— A pooled analysis of four randomized, active-controlled Phase 3 clinical trials presented at IDWeek 2012 has shown that moxifloxacin is an effective and safe option for secondary peritonitis.

Secondary peritonitis is an advanced form of complicated intra-abdominal infection that necessitates hospitalization, surgical source control, and empiric therapy. A broad-spectrum fluoroquinolone antibiotic, moxifloxacin is one of the recommended agents in the treatment of mild-to-moderate complicated intra-abdominal infections.

A post-hoc subgroup analysis of the four studies was conducted by Jan De Waele, MD, PhD, from Ghent University Hospital De Pintelaan, Ghent, Belgium. Three trials used a 10% non-inferiority margin, and one study used 15% non-inferiority margin. Patients studied had secondary peritonitis with an APACHE score of 7±5 that was community acquired (95.5%). The efficacy and safety of 400mg IV or IV/oral moxifloxacin was compared to comparators (ertapenem 1g IV daily, ceftriaxone 2g IV daily/metronidazole 500mg IV twice or three times daily, or piperacillin/tazobactam 3g/375mg IV four times daily plus oral amoxicillin/clavulanic acid 800mg/114mg twice or three times daily. An intent-to-treat population consisted of 1,229 patients. Clinical response and safety were evaluated at test-of-cure (11–45 days after treatment).

Moxifloxacin demonstrated comparable overall clinical success rates vs. the comparators studied at test-of-cure, both in a per-protocol population (moxifloxacin: 85.3% [range 74.2%–90.7%] vs. comparators: 88.4% [range 78.1%–94%], point estimate for the difference in success rates: -3%, 95% CI: -7.06–1.05) and in an intent-to-treat population (moxifloxacin: 73.7% [range 53.5%–82.3%] vs. comparators: 77.7% [range 51.6%–90.3%], point estimate for the difference in success rates: -3.96%, 95% CI: -8.54–0.61).

For a per-protocol population, similar clinical cure rates were seen in gallbladder and biliary tract infections (100% of 26 moxifloxacin patients vs. 96.6% of 29 comparator patients), stomach or duodenal infections (86.8% of 91 moxifloxacin patients vs. 92.9% of 98 comparator patients), appendicitis (85.1% of 269 moxifloxacin patients vs. 92.1% of 265 comparator patients), large bowel infections, (81.4% of 86 moxifloxacin patients vs. 73.8% of comparator patients), small bowel infections (80.6% of 31 moxifloxacin patients vs. 80% of 40 comparator patients), and other/unknown sites (100% of 2 moxifloxacin patients vs. 71.4% of 7 comparator patients).

In an intent-to-treat population, there was no clinically meaningful variation with moxifloxacin vs. comparators in adverse event incidence (67.3% for moxifloxacin vs. 59.8% for comparator), adverse drug reactions (20.9% for moxifloxacin vs. 20% for comparator) or deaths (4.3% for moxifloxacin vs. 3.4% for comparator).