Clinical Study of Cefiderocol (S-649266) for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens
Condition: Healthcare-associated Pneumonia (HCAP); Hospital Acquired Pneumonia (HAP); Ventilator Associated Pneumonia (VAP)
MeSH terms: Pneumonia; Pneumonia, Ventilator-Associated; Healthcare-Associated Pneumonia
Intervention: Cefiderocol; Meropenem; Linezolid
Intervention description: 2000 mg intravenously every 8 hours for a period of 7 to14 days (dosage adjustment is necessary based on renal function); 2000 mg intravenously every 8 hours for a period of 7 to 14 days (dosage adjustment is necessary based on renal function); 600 mg of linezolid administered intravenously over 30 minutes to 2 hours, every 12 hours.
Intervention MeSH terms: Meropenem; Linezolid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hospital-acquired pneumonia (HAP); S-649266; linezolid; meropenem; Healthcare-associated pneumonia (HCAP); nosocomial pneumonia; Ventilator-associated pneumonia (VAP); Gram-negative pathogens; pneumonia; cefiderocol

Summary:

      The primary objective of this study is to compare all-cause mortality at Day 14 in
      participants receiving cefiderocol with participants receiving the comparator, meropenem, in
      adults with hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial
      pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP) caused by
      Gram-negative pathogens.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects 18 years or older at the time of signing informed consent

          -  Subjects who have provided written informed consent or their informed consent has been
             provided by a legally authorized representative

          -  Subjects who meet the clinical diagnosis criteria for hospital-acquired bacterial
             pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or
             healthcare-associated bacterial pneumonia (HCABP)

          -  All subjects must fulfill at least 1 of the following clinical criteria at screening:

               1. New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea,
                  tachypnea (eg, respiratory rate > 25 breaths/minute), expectorated sputum
                  production, or requirement for mechanical ventilation

               2. Hypoxemia (eg, a partial pressure of oxygen [PaO2] < 60 mm Hg while the subject
                  is breathing room air, as determined by arterial blood gas [ABG], or worsening of
                  the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2])

               3. Need for acute changes in the ventilator support system to enhance oxygenation,
                  as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in
                  the amount of positive end-expiratory pressure

               4. New onset of or increase in (quantity or characteristics) suctioned respiratory
                  secretions, demonstrating evidence of inflammation and absence of contamination

          -  All subjects must have at least 1 of the following signs:

               1. Documented fever (ie, core body temperature [tympanic, rectal, esophageal] ≥ 38°C
                  [100.4°F], oral temperature ≥ 37.5°C, or axillary temperature ≥ 37°C)

               2. Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] ≤ 35°C
                  [95.0°F], oral temperature ≤ 35.5°C and axillary temperature ≤ 36°C)

               3. Leukocytosis with a total peripheral white blood cell (WBC) count ≥ 10,000
                  cells/mm³

               4. Leukopenia with total peripheral WBC count ≤ 4500 cells/mm³

               5. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear

          -  All subjects must have a chest radiograph during screening showing the presence of new
             or progressive infiltrate(s) suggestive of bacterial pneumonia. A computed tomography
             (CT) scan in the same time window showing the same findings could also be acceptable

          -  All subjects must have a suspected Gram-negative infection involving the lower
             respiratory tract

        Exclusion Criteria:

          -  Subjects who have known or suspected community-acquired bacterial pneumonia (CABP),
             atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of
             gastric contents, inhalation injury)

          -  Other exclusions based on the prescribing information of meropenem or linezolid, prior
             antibiotic usage, age, and pregnancy.