In a seriously ill patient population with HABP and VABP, Fetroja demonstrated non-inferiority vs extended-infusion, high-dose meropenem1

Studied in a multicenter, double-blind, randomized trial vs meropenem in HABP/VABP1,2

  • Study was designed to assess Fetroja use in nosocomial pneumonia in a non-inferiority trial*
    • Patients with HABP, VABP, and HCABP were included (N=298)
  • At time of randomization, patients with a carbapenem-resistant Gram-negative infection (if known) were excluded
  • The study evaluated a seriously ill nosocomial pneumonia population
    • Patients had a mean APACHE II score of 16; 49% of patients had a score of ≥16
    • 60% of patients were ventilated, while 68.2% were in the ICU
    • Approximately 33% had failed empiric treatment, a marker for drug resistance
  • The top 5 baseline Gram-negative pathogens were K pneumoniae, P aeruginosa, A baumannii, E coli, and E cloacae
  • ~30% of patients in both arms had ESBL-producing bacterial isolates at baseline

Meropenem was used as a comparator in the trial and was optimized (2 g IV over 3 h q8h) for seriously ill patients with a multidrug-resistant Gram-negative infection in the ICU1,3,4

  • Was higher than other similar nosocomial pneumonia clinical studies (1 gram)

Assessments1,2

* All patients received Gram-positive treatment with linezolid for at least 5 days.
Study was initiated before Infectious Diseases Society of America/American Thoracic Society guidance to remove HCABP from HABP/VABP category.5

Primary and key secondary endpoints

In a seriously ill patient population with HABP and VABP, Fetroja demonstrated non-inferiority vs extended-infusion, high-dose meropenem1
Endpoint (Modified intent-to-treat population [mITT])a Fetroja % (n/N) Meropenem % (n/N) Treatment differenceb (95% CI)
Day 14 all-cause mortality rate (Primary endpoint) 12.4%
(18/145)
12.2%
(18/147)
0.2
(-7.2, 7.7)
Key secondary endpoints
Day 28 all-cause mortality rate 22.1%
(32/145)
21.1%
(31/147)
1.1
(-8.2, 10.4)
Clinical cure at TOCc 64.8%
(94/145)
66.7%
(98/147)
-2.0
(-12.5, 8.5)
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a mITT population included all randomized patients who received study medication with evidence of bacterial pneumonia, except those with only anaerobic or Gram-positive aerobic infections.1
b The adjusted treatment difference (Fetroja minus meropenem) and associated 95% CI were based on the Cochran-Mantel-Haenszel stratum-weighted method. Subjects with unknown survival status were considered deaths. For Day 14 all-cause mortality, 1 meropenem subject had unknown status; for Day 28 all-cause mortality, 1 meropenem subject and 2 Fetroja subjects had unknown status.1
c Clinical cure was defined as resolution or substantial improvement in signs and symptoms associated with pneumonia, such that no additional antibacterial therapy was required for the treatment of the current infection through the TOC visit.1
Fetroja is the first cephalosporin to have a clinical indication for A baumannii complex.1
The treatment difference in all-cause mortality for patients with several pathogens, including K pneumoniae, P aeruginosa, and A baumannii, remained consistent for Fetroja and extended-infusion, high-dose meropenem at Day 14 and Day 28.1
All-cause mortality rate was similar for Fetroja vs extended-infusion, high-dose meropenem against ESBL-producing bacteria in the mITT population.1
Fetroja showed clinical efficacy against pathogens with several key carbapenem-resistant mechanisms, including metallo-carbapenemases (IMP, VIM, and NDM) and serine-carbapenemases (OXA-48, OXA-23)2*
* Post-randomization, carbapenem-resistant infections were detected.

Adverse reactions

Fetroja adverse reactions vs extended-infusion, high-dose meropenem in HABP and VABP1

Serious adverse reactions and adverse reactions leading to discontinuation
Adverse reaction (safety populationd) Fetroja (n=148) Extended-infusion, high-dose meropenem (n=150)
Serious adverse reactions 36.5% 30.0%
Death 26.4% 23.3%
Discontinuation of treatment due to adverse reaction 8.1% 9.3%
Selected adverse reactions occurring in ≥4% of patients receiving Fetroja in the HABP/VABP trial
Adverse reaction Fetrojae (n=148) Extended-infusion, high-dose meropenemf (n=150)
Elevations in liver testsg 16% 16%
Hypokalemiah 11% 15%
Diarrhea 9% 9%
Hypomagnesemia 5% <1%
Atrial fibrillation 5% 3%
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d Safety population: all randomized subjects who received at least 1 dose of the study treatment (Fetroja, n=148, and extended infusion, high-dose meropenem, n=150).1,2
e 2 grams IV over 3 hours every 8 hours (with dosing adjustment based on renal function).
f 2 grams IV over 3 hours every 8 hours (with dosing adjustment based on renal function).
g Elevations in liver tests include the following terms: aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyl transferase increased, liver function test increased, liver function test abnormal, hepatic enzyme increased, transaminases increased, hypertransaminesemia.
h Hypokalemia includes blood potassium decreased.