Roman Stets1, Monica Popescu1, Joven R Gonong1, Ismail Mitha1, William Nseir1, Andrzej Madej1, Courtney Kirsch1, Anita F Das1, Lynne Garrity-Ryan1, Judith N Steenbergen1, Amy Manley1, Paul B Eckburg1, Evan Tzanis1, Paul C McGovern1, Evan Loh1. 1. From City Clinical Hospital #6, Zaporizhzhia, Ukraine (R.S.); Sf. Pantelimon Clinical Emergency Hospital, Bucharest, Romania (M.P.); Lung Center of the Philippines, Manila (J.R.G.); Lakeview Hospital, Benoni, South Africa (I.M.); EMMS, Nazareth Hospital, Nazareth, and Faculty of Medicine in the Galilee, Bar-Ilan University, Safed - both in Israel (W.N.); the Department of Internal Medicine and Pharmacology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland (A. Madej); AD Stats Consulting, Guerneville, CA (A.F.D.); and Paratek Pharmaceuticals, King of Prussia, PA (C.K., L.G.-R., J.N.S., A. Manley, P.B.E., E.T., P.C.M., E.L.).
Abstract
BACKGROUND:Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia. METHODS: In a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used. RESULTS: The intention-to-treat population included 386 patients in the omadacycline group and 388 patients in themoxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, -1.6 percentage points; 95% confidence interval [CI], -7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, -2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial. CONCLUSIONS:Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438 .).
RCT Entities:
BACKGROUND:Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia. METHODS: In a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used. RESULTS: The intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, -1.6 percentage points; 95% confidence interval [CI], -7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, -2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial. CONCLUSIONS:Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438 .).
Authors: Michael A Pfaller; Michael D Huband; Dee Shortridge; Robert K Flamm Journal: Antimicrob Agents Chemother Date: 2020-04-21 Impact factor: 5.191
Authors: D C Richter; T Brenner; A Brinkmann; B Grabein; M Hochreiter; A Heininger; D Störzinger; J Briegel; M Pletz; M A Weigand; C Lichtenstern Journal: Anaesthesist Date: 2019-11 Impact factor: 1.041
Authors: David M P De Oliveira; Brian M Forde; Timothy J Kidd; Patrick N A Harris; Mark A Schembri; Scott A Beatson; David L Paterson; Mark J Walker Journal: Clin Microbiol Rev Date: 2020-05-13 Impact factor: 26.132