SOLITAIRE-IV: A Randomized, Double-Blind, Multi-Center Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-acquired Bacterial Pneumonia.
Clin Infect Dis. 2016 Jul 22;
Authors: File TM, Rewerska B, Vucinić-Mihailović V, Gonong JR, Das AF, Keedy K, Taylor D, Sheets A, Fernandes P, Oldach D, Jamieson BD, SOLITAIRE-IV Pneumonia Team
BACKGROUND: Solithromycin, a novel macrolide antibiotic with both intravenous (IV) and oral formulations dosed once daily, has completed two global Phase 3 trials for treatment of community-acquired bacterial pneumonia (CABP).
METHODS: 863 adults with CABP (PORT II-IV) were randomized 1:1 to receive either IV-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg IV on Day 1 and were permitted to switch to oral dosing when clinically indicated. The primary objective was to demonstrate non-inferiority (NI, 10% margin) of solithromycin to moxifloxacin in achievement of early clinical response (ECR) assessed 3 days after first dose in the intent-to-treat (ITT) population. Secondary endpoints included demonstrating NI in ECR in the microbiological ITT population (mITT) and determination of investigator-assessed success rates at the short-term follow-up (SFU) visit 5-10 days post-therapy.
RESULTS: In the ITT population, 79.3% of solithromycin patients and 79.7% of moxifloxacin patients achieved ECR (treatment difference: -0.46; 95% CI: -6.1, 5.2). In the mITT population, 80.3% of solithromycin patients and 79.1% of moxifloxacin patients achieved ECR (treatment difference: 1.26; 95% CI: -8.1, 10.6). In the ITT population, 84.6% of solithromycin patients and 88.6% of moxifloxacin patients achieved clinical success at SFU based on investigator assessment. Mostly mild/moderate infusion events led to higher incidence of adverse events overall in the solithromycin group. Other adverse events were comparable between treatment groups.
CONCLUSIONS: IV-to-oral solithromycin was non-inferior to IV-to-oral moxifloxacin. Solithromycin has potential to provide an IV and oral option for monotherapy for CABP.
CLINICAL TRIALS REGISTRATION: NCT01968733.
PMID: 27448679 [PubMed - as supplied by publisher]