Clinical Study of Cefiderocol (S-649266) for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens (APEKS-NP)

Shionogi

Status and phase: Completed; Phase 3

Conditions: Healthcare-associated Pneumonia (HCAP); Ventilator Associated Pneumonia (VAP); Hospital Acquired Pneumonia (HAP)

Treatments: Drug: Linezolid; Drug: Cefiderocol; Drug: Meropenem

Study type: Interventional

Funder types: Industry

Identifiers

NCT03032380

2016-003020-23 (EudraCT Number)

1615R2132

Details and patient eligibility

About

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.

Enrollment: 300 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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300 participants in 2 patient groups

Cefiderocol

Experimental group

Description:

Participants will receive 2 g cefiderocol administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Treatment:

Drug: Cefiderocol

Drug: Linezolid

Meropenem

Active Comparator group

Description:

Participants will receive 2 g meropenem administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.

Treatment:

Drug: Meropenem

Drug: Linezolid