title: Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial: A Randomized Clinical Trial.
abstract: Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class with in vitro activity against clinically important gram-negative, gram-positive aerobic, and facultative bacteria including most of those resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug resistant strains and carbapenem-resistant Enterobacteriaceae, and most anaerobic pathogens.
  
  
  
  To evaluate the efficacy and safety of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs).
  
  
  
  This was a phase III, randomized, double-blind, multicenter study that evaluated the efficacy and safety of eravacycline in comparison with ertapenem in patients with cIAI requiring surgical or percutaneous intervention. The test-of-cure evaluation was conducted 25 to 31 days after the first dose of the study drug and the follow-up visit was conducted 38 to 50 days after the first dose of the study drug. All patients recruited into this study were hospitalized. Five hundred forty-one patients were recruited for this study; 270 patients were randomized to receive eravacycline, and 271 patients were randomized to receive ertapenem. Patients had to meet all of the following criteria: hospitalized for cIAI requiring intervention; 18 years or older; evidence of systemic inflammatory response; pain caused by cIAI; able to provide informed consent; and diagnosis of cIAI with sonogram or radiographic imaging or visual confirmation. Analyses were done in intent-to-treat and evaluable populations.
  
  
  
  Patients received eravacycline, 1.0 mg/kg every 12 hours, or ertapenem, 1.0 g every 24 hours, for a minimum of four 24-hour dosing cycles.
  
  
  
  Clinical outcome assessments were made at the end of treatment, test of cure, and follow-up visits and were classified as clinical cure, clinical failure, or indeterminate/missing.
  
  
  
  In total, 541 patients were randomly assigned to treatment: 270 in the eravacycline group and 271 in the ertapenem group. The mean ages were 54.9 years and 55.4 years for the eravacycline and ertapenem groups, respectively. Most patients were white (263 of 270 patients [97.4%] in the eravacycline group and 260 of 271 patients [95.9%] in the ertapenem group). For the microbiological intent-to-treat population, the rates of clinical cure at the test-of-cure visit were 86.8% in the eravacycline group and 87.6% in the ertapenem group. The difference in clinical cure rates between the groups was -0.80% (95% CI, -7.1% to 5.5%), meeting the prespecified noninferiority margin and allowing for statistical noninferiority of eravacycline to ertapenem to be declared for this study. Both study drugs were well tolerated.
  
  
  
  Overall, eravacycline demonstrated noninferiority to ertapenem for the treatment of patients with cIAI.
  
  
  
  Clinicaltrials.gov Identifier: NCT01844856.
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Joseph
authors.initials: J
authors.lastname: Solomkin
authors.affiliation: Ohio State University School of Medicine, Columbus.
authors.forename: David
authors.initials: D
authors.lastname: Evans
authors.affiliation: Klaipeda University Hospital, Klaipeda, Lithuania.
authors.forename: Algirdas
authors.initials: A
authors.lastname: Slepavicius
authors.affiliation: Baystate Medical Center, Springfield, Massachusetts.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lee
authors.affiliation: Tetraphase Pharmaceuticals Inc, Watertown, Massachusetts.
authors.forename: Andrew
authors.initials: A
authors.lastname: Marsh
authors.affiliation: Tetraphase Pharmaceuticals Inc, Watertown, Massachusetts.
authors.forename: Larry
authors.initials: L
authors.lastname: Tsai
authors.affiliation: Tetraphase Pharmaceuticals Inc, Watertown, Massachusetts.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Sutcliffe
authors.affiliation: Tetraphase Pharmaceuticals Inc, Watertown, Massachusetts.
authors.forename: Patrick
authors.initials: P
authors.lastname: Horn
mesh_terms: D018784:Abdominal Abscess / Q000188:drug therapy* / Q000382:microbiology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001064:Appendicitis / Q000150:complications; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D000077727:Ertapenem; D005260:Female; D006090:Gram-Negative Bacteria; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology; D013754:Tetracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D047090:beta-Lactams / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D013754:Tetracyclines; D047090:beta-Lactams; C571179:eravacycline; D000077727:Ertapenem