A double-blind trial published in the New England Journal of Medicine found omadacycline to be noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (ClincalTrials.gov identifier: NCT02531438).
The double-blind trial randomly assigned adult patients with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) in a 1:1 ratio to receive either omadacycline or moxifloxacin for 7 to 14 days. Participants received either 2 doses of 100 mg omadacycline intravenously every 12 hours and then 100 mg intravenously every 24 hours, or 400 mg moxifloxacin intravenously every 24 hours. Transient oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours) was allowed after 3 days of treatment.
The primary endpoint for this trial was early clinical response, defined as survival with improvement in at least 2 of 4 symptoms and no worsening of symptoms at 72 or 120 hours, without the need for rescue antibacterial therapy. The 4 included symptoms were cough, sputum production, pleuritic chest pain, and dyspnea. An investigator-assessed clinical response of resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary 5 to 10 days after the last dose was used as a secondary endpoint, along with a noninferiority margin of 10%.
The intention-to-treat populations for the omadacycline and moxifloxacin groups were 386 and 388 patients, respectively. For early clinical response, omadacycline was noninferior to moxifloxacin (81.1% and 82.7%, respectively; difference −1.6%; 95% CI, −7.1% to 3.8%). The rates of posttreatment clinical response were 87.6% for participants in the omadacycline group and 85.1% for the moxifloxacin group (difference, 2.5%; 95% CI, −2.4% to 7.4%). Adverse events were reported in 41.1% of the omadacycline group and 48.5% of the moxifloxacin group, the most frequent of which were gastrointestinal.
Investigators excluded or limited the inclusion of patients who were immunocompromised and those with severe pneumonia, which reduced the generalizability of the results. The same was done for patients with pneumonia severity index risk class I or II because they have fewer risks for death, and therefore are less commonly admitted to hospital for initial treatment than those at higher risk. Extensive microbiologic testing in this trial resulted in a bacterial pathogen being identified in 50% of patients. According to investigators, real-world cases of community-acquired bacterial pneumonia are identified approximately 10% of the time; therefore, empirical therapy, “must be chosen with common respiratory pathogens and contemporary local susceptibility taken into consideration.”
The results led investigators to conclude that intravenous, once-daily omadacycline, with the option to transition to oral administration, was “noninferior to moxifloxacin as empirical monotherapy for non-ICU hospitalized adults with community-acquired bacterial pneumonia.”
Trial funded by Paratek Pharmaceuticals.
Stets R, Popescu M, Gonong JR, et al. Omadacycline for community-acquired bacterial pneumonia. New Engl J Med. 2019;380:517-527.