Phase 3
N=300
Clinical Study of Cefiderocol (S-649266) for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens
Healthcare-associated Pneumonia (HCAP) · Hospital Acquired Pneumonia (HAP) · Ventilator Associated Pneumonia (VAP)
Bottom Line
View on ClinicalTrials.gov: NCT03032380 ↗Enrolled (actual)
300
Serious AEs
33.2%
Results posted
Nov 2020
Primary outcome: Primary: All-cause Mortality Rate at Day 14 — 12.4; 11.6 percentage of participants — p=0.0020
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cefiderocol (Drug); Meropenem (Drug); Linezolid (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Shionogi
- Primary completion
- Feb 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY All-cause Mortality Rate at Day 14 |
12.4; 11.6 | 0.0020 sig |
| SECONDARY Percentage of Participants With Microbiologic Eradication at Test of Cure (TOC) |
47.6; 48.0 | — |
| SECONDARY Percentage of Participants With Clinical Cure at Test of Cure |
64.8; 66.7 | — |
| SECONDARY Percentage of Participants With Clinical Cure at Early Assessment (EA) |
82.8; 83.0 | — |
| SECONDARY Percentage of Participants With Clinical Cure at End of Treatment (EOT) |
77.2; 81.0 | — |
| SECONDARY Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) |
57.9; 57.8 | — |
| SECONDARY Percentage of Participants With Microbiologic Eradication at Early Assessment |
41.9; 53.5 | — |
| SECONDARY Percentage of Participants With Microbiologic Eradication at End of Treatment |
63.7; 66.9 | — |
| SECONDARY Percentage of Participants With Sustained Microbiologic Eradication at Follow-up |
43.5; 38.6 | — |
| SECONDARY All-cause Mortality Rate at Day 28 |
21.0; 20.5 | — |
| SECONDARY All-cause Mortality Rate at the End of Study |
26.8; 23.3 | — |
| SECONDARY Total Hospitalization Time |
11.54; 11.47; 13.49; 12.98 | 0.9382 |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events |
130; 129; 33; 37; 41; 47 | — |
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:
- 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
- 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])
- 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
- 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:
- Documented fever (ie, core body temperature [tympanic, rectal, esophageal] ≥ 38°C [100.4°F], oral temperature ≥ 37.5°C, or axillary temperature ≥ 37°C)
- Hypothermia (ie, core body temperature [tympanic, rectal, esophageal] ≤ 35°C [95.0°F], oral temperature ≤ 35.5°C and axillary temperature ≤ 36°C)
- Leukocytosis with a total peripheral white blood cell (WBC) count ≥ 10,000 cells/mm³
- Leukopenia with total peripheral WBC count ≤ 4500 cells/mm³
- 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.
Data sourced from ClinicalTrials.gov (NCT03032380). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.