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

Primary Purpose

Healthcare-associated Pneumonia (HCAP), Hospital Acquired Pneumonia (HAP), Ventilator Associated Pneumonia (VAP)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cefiderocol
Meropenem
Linezolid
Sponsored by
Shionogi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthcare-associated Pneumonia (HCAP) focused on measuring Hospital-acquired pneumonia (HAP), S-649266, linezolid, meropenem, Healthcare-associated pneumonia (HCAP), nosocomial pneumonia, Ventilator-associated pneumonia (VAP), Gram-negative pathogens, pneumonia, cefiderocol

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Shionogi Research Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cefiderocol

Meropenem

Arm 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.

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.

Outcomes

Primary Outcome Measures

All-cause Mortality Rate at Day 14
The all-cause mortality (ACM) rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from the first infusion of study drug up to Day 14. The Modified Intent-to-Treat Population included all randomized participants who met either of the following criteria: Evidence of Gram-negative infection of the lower respiratory tract based on a culture, Gram-stain, or other diagnostic test Evidence of a lower respiratory tract infection but culture or other diagnostic tests did not provide a microbiologic diagnosis

Secondary Outcome Measures

Percentage of Participants With Microbiologic Eradication at Test of Cure (TOC)
Lower respiratory tract specimens (eg, sputum, endotracheal aspiration [ETA], endobronchial culture specimens collected by bronchoalveolar lavage [BAL], or protected specimen brush [PSB], lung biopsy tissue, pleural effusions, etc) were sent to the local microbiology laboratory for isolation and identification of pathogens. Microbiological outcome by Baseline pathogen at TOC was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, bronchoalveolar lavage (BAL) fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture, and the participant had a successful clinical outcome, the response was presumed as eradication.
Percentage of Participants With Clinical Cure at Test of Cure
Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate. Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.
Percentage of Participants With Clinical Cure at Early Assessment (EA)
Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate. Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.
Percentage of Participants With Clinical Cure at End of Treatment (EOT)
Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate. Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.
Percentage of Participants With Sustained Clinical Cure at Follow-up (FU)
Clinical outcome was assessed by the investigator at follow-up as either Sustained Clinical Cure, Relapse, or Indeterminate. Sustained Clinical Cure: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC.
Percentage of Participants With Microbiologic Eradication at Early Assessment
Microbiological outcome by Baseline pathogen at Early Assessment was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture, and the participant had a successful clinical outcome, the response was presumed as eradication.
Percentage of Participants With Microbiologic Eradication at End of Treatment
Microbiological outcome by Baseline pathogen at End of Treatment was determined by the sponsor as either: Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture, and the participant had a successful clinical outcome, the response was presumed as eradication.
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up
Microbiological outcome by Baseline pathogen at Follow-up was determined by the sponsor as either Sustained Eradication, Persistence, Recurrence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Sustained eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy) after TOC. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical response after TOC, the response was presumed to be eradication.
All-cause Mortality Rate at Day 28
The all-cause mortality (ACM) rate at Day 28 was calculated as the percentage of participants who experienced mortality, regardless of the cause, from the first dose of study drug up to Day 28.
All-cause Mortality Rate at the End of Study
The all-cause mortality rate during both the treatment and follow-up period (up to the end of study [EOS] visit) was calculated as the percentage of participants who experienced mortality, regardless of the cause, from the first infusion of study drug up to EOS. If a participant discontinued from the study before EOS and survival information was not available, then the survival status for this endpoint for the participant was considered unknown.
Total Hospitalization Time
The length of hospital stay attributable to the study-qualifying infection.
Number of Participants With Treatment-Emergent Adverse Events
The severity of each adverse event (AE) was graded by the investigator according to the following definitions: Mild: A finding or symptom is minor and does not interfere with usual daily activities. Moderate: The event causes discomfort and interferes with usual daily activity or affects clinical status. Severe: The event causes an interruption of the participant's usual daily activities or has a clinically significant effect. The relationship of each AE to the study treatment was determined by the investigator based on whether the AE could be reasonably explained as having been caused by the study drug (treatment related AE [TRAE]). An SAE is defined as any AE occurring at any dose that resulted in any of the following outcomes: Death Life-threatening condition Hospitalization or prolongation of existing hospitalization for treatment Persistent or significant disability/incapacity Congenital anomaly/birth defect Other medically important condition

Full Information

First Posted
January 17, 2017
Last Updated
October 20, 2020
Sponsor
Shionogi
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1. Study Identification

Unique Protocol Identification Number
NCT03032380
Brief Title
Clinical Study of Cefiderocol (S-649266) for the Treatment of Nosocomial Pneumonia Caused by Gram-negative Pathogens
Acronym
APEKS-NP
Official Title
A Multicenter, Randomized, Double-blind, Parallel-group, Clinical Study of S-649266 Compared With Meropenem for the Treatment of Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, or Healthcare-associated Bacterial Pneumonia Caused by Gram-negative Pathogens
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
October 24, 2017 (Actual)
Primary Completion Date
February 26, 2019 (Actual)
Study Completion Date
April 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shionogi

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthcare-associated Pneumonia (HCAP), Hospital Acquired Pneumonia (HAP), Ventilator Associated Pneumonia (VAP)
Keywords
Hospital-acquired pneumonia (HAP), S-649266, linezolid, meropenem, Healthcare-associated pneumonia (HCAP), nosocomial pneumonia, Ventilator-associated pneumonia (VAP), Gram-negative pathogens, pneumonia, cefiderocol

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
300 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cefiderocol
Arm Type
Experimental
Arm 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.
Arm Title
Meropenem
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Cefiderocol
Other Intervention Name(s)
S-649266
Intervention Description
2000 mg intravenously every 8 hours for a period of 7 to14 days (dosage adjustment is necessary based on renal function)
Intervention Type
Drug
Intervention Name(s)
Meropenem
Other Intervention Name(s)
Merrem®
Intervention Description
2000 mg intravenously every 8 hours for a period of 7 to 14 days (dosage adjustment is necessary based on renal function)
Intervention Type
Drug
Intervention Name(s)
Linezolid
Other Intervention Name(s)
Zyvox®
Intervention Description
600 mg of linezolid administered intravenously over 30 minutes to 2 hours, every 12 hours.
Primary Outcome Measure Information:
Title
All-cause Mortality Rate at Day 14
Description
The all-cause mortality (ACM) rate at Day 14 was calculated as the percentage of participants in each treatment group who experienced mortality, regardless of the cause, from the first infusion of study drug up to Day 14. The Modified Intent-to-Treat Population included all randomized participants who met either of the following criteria: Evidence of Gram-negative infection of the lower respiratory tract based on a culture, Gram-stain, or other diagnostic test Evidence of a lower respiratory tract infection but culture or other diagnostic tests did not provide a microbiologic diagnosis
Time Frame
From first dose of study drug to Day 14
Secondary Outcome Measure Information:
Title
Percentage of Participants With Microbiologic Eradication at Test of Cure (TOC)
Description
Lower respiratory tract specimens (eg, sputum, endotracheal aspiration [ETA], endobronchial culture specimens collected by bronchoalveolar lavage [BAL], or protected specimen brush [PSB], lung biopsy tissue, pleural effusions, etc) were sent to the local microbiology laboratory for isolation and identification of pathogens. Microbiological outcome by Baseline pathogen at TOC was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, bronchoalveolar lavage (BAL) fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture, and the participant had a successful clinical outcome, the response was presumed as eradication.
Time Frame
Test of cure (7 days after end of treatment; equivalent to Study Day 14 to 21)
Title
Percentage of Participants With Clinical Cure at Test of Cure
Description
Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate. Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.
Time Frame
Test of cure (7 days after the end of treatment; equivalent to Study Day 14 to 21)
Title
Percentage of Participants With Clinical Cure at Early Assessment (EA)
Description
Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate. Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.
Time Frame
Early assessment (Day 3-4 after the start of treatment)
Title
Percentage of Participants With Clinical Cure at End of Treatment (EOT)
Description
Clinical outcome was assessed by the investigator as either Clinical Cure, Clinical Failure, or Indeterminate. Clinical Cure: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia, including a reduction in Sequential Organ Failure Assessment (SOFA) and Clinical Pulmonary Infection Score (CPIS) scores, and improvement or lack of progression of chest radiographic abnormalities such that no additional antibacterial therapy was required for the treatment of the current infection.
Time Frame
End of treatment (Day 7 to 14)
Title
Percentage of Participants With Sustained Clinical Cure at Follow-up (FU)
Description
Clinical outcome was assessed by the investigator at follow-up as either Sustained Clinical Cure, Relapse, or Indeterminate. Sustained Clinical Cure: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy was required for the treatment of pneumonia in a participant assessed as cured at TOC.
Time Frame
Follow-up (14 days after the end of treatment; Day 21 to 28)
Title
Percentage of Participants With Microbiologic Eradication at Early Assessment
Description
Microbiological outcome by Baseline pathogen at Early Assessment was determined by the sponsor as either Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture, and the participant had a successful clinical outcome, the response was presumed as eradication.
Time Frame
Early Assessment, Days 3 to 4
Title
Percentage of Participants With Microbiologic Eradication at End of Treatment
Description
Microbiological outcome by Baseline pathogen at End of Treatment was determined by the sponsor as either: Eradication, Persistence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy). If it was not possible to obtain an appropriate clinical culture, and the participant had a successful clinical outcome, the response was presumed as eradication.
Time Frame
End of treatment, Day 7 to 14
Title
Percentage of Participants With Sustained Microbiologic Eradication at Follow-up
Description
Microbiological outcome by Baseline pathogen at Follow-up was determined by the sponsor as either Sustained Eradication, Persistence, Recurrence, or Indeterminate. Overall per-participant microbiological outcome was determined based on the individual microbiological outcomes for each Baseline pathogen. Sustained eradication: Absence of all Baseline Gram-negative pathogens from an appropriate clinical specimen (sputum, tracheal aspirate, BAL fluid, protected specimen brush, pleural fluid, or lung biopsy) after TOC. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical response after TOC, the response was presumed to be eradication.
Time Frame
Follow-up (14 days after the end of treatment, Days 21 to 28)
Title
All-cause Mortality Rate at Day 28
Description
The all-cause mortality (ACM) rate at Day 28 was calculated as the percentage of participants who experienced mortality, regardless of the cause, from the first dose of study drug up to Day 28.
Time Frame
From first dose of study drug to Day 28
Title
All-cause Mortality Rate at the End of Study
Description
The all-cause mortality rate during both the treatment and follow-up period (up to the end of study [EOS] visit) was calculated as the percentage of participants who experienced mortality, regardless of the cause, from the first infusion of study drug up to EOS. If a participant discontinued from the study before EOS and survival information was not available, then the survival status for this endpoint for the participant was considered unknown.
Time Frame
From first dose of study drug through end of study (28 days after end of treatment, up to 42 days)
Title
Total Hospitalization Time
Description
The length of hospital stay attributable to the study-qualifying infection.
Time Frame
From first dose of study drug to test of cure (7 days after end of treatment; equivalent to Study Day 14 to 21) and to follow-up (14 days after the end of treatment; Day 21 to 28)
Title
Number of Participants With Treatment-Emergent Adverse Events
Description
The severity of each adverse event (AE) was graded by the investigator according to the following definitions: Mild: A finding or symptom is minor and does not interfere with usual daily activities. Moderate: The event causes discomfort and interferes with usual daily activity or affects clinical status. Severe: The event causes an interruption of the participant's usual daily activities or has a clinically significant effect. The relationship of each AE to the study treatment was determined by the investigator based on whether the AE could be reasonably explained as having been caused by the study drug (treatment related AE [TRAE]). An SAE is defined as any AE occurring at any dose that resulted in any of the following outcomes: Death Life-threatening condition Hospitalization or prolongation of existing hospitalization for treatment Persistent or significant disability/incapacity Congenital anomaly/birth defect Other medically important condition
Time Frame
From first dose of study drug through the end of study, up to 42 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shionogi Clinical Trials Administrator Clinical Support Help Line
Organizational Affiliation
Shionogi
Official's Role
Study Director
Facility Information:
Facility Name
Shionogi Research Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Shionogi Research Site
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Shionogi Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Shionogi Research Site
City
Council Bluffs
State/Province
Iowa
ZIP/Postal Code
51503
Country
United States
Facility Name
Shionogi Research Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Shionogi Research Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Shionogi Research Site
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Shionogi Research Site
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21404
Country
United States
Facility Name
Shionogi Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Shionogi Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-0250
Country
United States
Facility Name
Shionogi Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Shionogi Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210-1267
Country
United States
Facility Name
Shionogi Research Site
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18105
Country
United States
Facility Name
Shionogi Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
Shionogi Research Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Shionogi Research Site
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Shionogi Research Site
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Shionogi Research Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H3A7
Country
Canada
Facility Name
Shionogi Research Site
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
Facility Name
Shionogi Research Site
City
Brno
ZIP/Postal Code
65693
Country
Czechia
Facility Name
Shionogi Research Site
City
Hradec Kralove
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Shionogi Research Site
City
Kolin
ZIP/Postal Code
28000
Country
Czechia
Facility Name
Shionogi Research Site
City
Kyjov
ZIP/Postal Code
69701
Country
Czechia
Facility Name
Shionogi Research Site
City
Ostrava-Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Shionogi Research Site
City
Prague
ZIP/Postal Code
15006
Country
Czechia
Facility Name
Shionogi Research Site
City
Pribram
ZIP/Postal Code
26101
Country
Czechia
Facility Name
Shionogi Research Site
City
Kohtla-Jarve
ZIP/Postal Code
31025
Country
Estonia
Facility Name
Shionogi Research Site
City
Parnu
ZIP/Postal Code
80010
Country
Estonia
Facility Name
Shionogi Research Site
City
Tallin
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Shionogi Research Site
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
Facility Name
Shionogi Research Site
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
Shionogi Research Site
City
Argenteuil
ZIP/Postal Code
95100
Country
France
Facility Name
Shionogi Research Site
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Shionogi Research Site
City
LaRoche-sur-Yon
ZIP/Postal Code
85925
Country
France
Facility Name
Shionogi Research Site
City
Lyon Cedex
ZIP/Postal Code
69437
Country
France
Facility Name
Shionogi Research Site
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Shionogi Research Site
City
Paris Cedex
ZIP/Postal Code
75018
Country
France
Facility Name
Shionogi Research Site
City
Batumi
ZIP/Postal Code
6010
Country
Georgia
Facility Name
Shionogi Research Site
City
Kutaisi
ZIP/Postal Code
4600
Country
Georgia
Facility Name
Shionogi Research Site
City
Kutaisi
ZIP/Postal Code
4601
Country
Georgia
Facility Name
Shionogi Research Site
City
Tbilisi
ZIP/Postal Code
0160
Country
Georgia
Facility Name
Shionogi Research Site
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Shionogi Research Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Shionogi Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Shionogi Research Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Shionogi Research Site
City
Budapest
ZIP/Postal Code
1121
Country
Hungary
Facility Name
Shionogi Research Site
City
Budapest
ZIP/Postal Code
1125
Country
Hungary
Facility Name
Shionogi Research Site
City
Debrecen
ZIP/Postal Code
H-4031
Country
Hungary
Facility Name
Shionogi Research Site
City
Fehergyarmat
ZIP/Postal Code
4900
Country
Hungary
Facility Name
Shionogi Research Site
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Shionogi Research Site
City
Holon
ZIP/Postal Code
58100
Country
Israel
Facility Name
Shionogi Research Site
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Shionogi Research Site
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Shionogi Research Site
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Shionogi Research Site
City
Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Shionogi Research Site
City
Maebashi
State/Province
Gunma
ZIP/Postal Code
371-8511
Country
Japan
Facility Name
Shionogi Research Site
City
Tsuchiura
State/Province
Ibaraki
ZIP/Postal Code
300-8585
Country
Japan
Facility Name
Shionogi Research Site
City
Tsu-city
State/Province
Mie
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Shionogi Research Site
City
Shimajiri-gun
State/Province
Okinawa
ZIP/Postal Code
901-1193
Country
Japan
Facility Name
Shionogi Research Site
City
Itabashi-ku
State/Province
Tokyo
ZIP/Postal Code
173-8610
Country
Japan
Facility Name
Shionogi Research Site
City
Kumamoto
ZIP/Postal Code
860-0008
Country
Japan
Facility Name
Shionogi Research Site
City
Daugavpils
ZIP/Postal Code
LV-5417
Country
Latvia
Facility Name
Shionogi Research Site
City
Liepaja
ZIP/Postal Code
LV-3414
Country
Latvia
Facility Name
Shionogi Research Site
City
Riga
ZIP/Postal Code
LV-1006
Country
Latvia
Facility Name
Shionogi Research Site
City
Saldus Novads
ZIP/Postal Code
LV-1002
Country
Latvia
Facility Name
Shionogi Research Site
City
Jaro
State/Province
Iloilo City
ZIP/Postal Code
5000
Country
Philippines
Facility Name
Shionogi Research Site
City
Tondo
State/Province
Manila
ZIP/Postal Code
1012
Country
Philippines
Facility Name
Shionogi Research Site
City
Caloocan
State/Province
Metro Manila
ZIP/Postal Code
1400
Country
Philippines
Facility Name
Shionogi Research Site
City
Quezon City
State/Province
Metro Manila
ZIP/Postal Code
1104
Country
Philippines
Facility Name
Shionogi Research Site
City
Quezon City
State/Province
Metro Manila
ZIP/Postal Code
1109
Country
Philippines
Facility Name
Shionogi Research Site
City
Caloocan City
ZIP/Postal Code
1427
Country
Philippines
Facility Name
Shionogi Research Site
City
Iloilo City
ZIP/Postal Code
5000
Country
Philippines
Facility Name
Shionogi Research Site
City
Manila
ZIP/Postal Code
1000
Country
Philippines
Facility Name
Shionogi Research Site
City
San Juan
ZIP/Postal Code
00921
Country
Puerto Rico
Facility Name
Shionogi Research Site
City
Barnaul
ZIP/Postal Code
656024
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Barnaul
ZIP/Postal Code
656045
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Chelyabinsk
ZIP/Postal Code
454000
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Krasnodar
ZIP/Postal Code
350012
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Moscow
ZIP/Postal Code
105203
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Moscow
ZIP/Postal Code
115280
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Moscow
ZIP/Postal Code
127015
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Novosibirsk
ZIP/Postal Code
630051
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Novosibirsk
ZIP/Postal Code
630075
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Sait-Petersburg
ZIP/Postal Code
194354
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Smolensk
ZIP/Postal Code
214019
Country
Russian Federation
Facility Name
Shionogi Research Site
City
St. Petersburg
ZIP/Postal Code
192242
Country
Russian Federation
Facility Name
Shionogi Research Site
City
St. Petersburg
ZIP/Postal Code
196247
Country
Russian Federation
Facility Name
Shionogi Research Site
City
St. Petersburg
ZIP/Postal Code
197706
Country
Russian Federation
Facility Name
Shionogi Research Site
City
St. Petersburg
ZIP/Postal Code
454091
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Tomsk
ZIP/Postal Code
634063
Country
Russian Federation
Facility Name
Shionogi Research Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Shionogi Research Site
City
Kragujev Ac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
Shionogi Research Site
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
Shionogi Research Site
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Shionogi Research Site
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Shionogi Research Site
City
Barcelona
ZIP/Postal Code
08026
Country
Spain
Facility Name
Shionogi Research Site
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Shionogi Research Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Shionogi Research Site
City
Madrid
ZIP/Postal Code
28922
Country
Spain
Facility Name
Shionogi Research Site
City
Torrejon de Ardoz
ZIP/Postal Code
28850
Country
Spain
Facility Name
Shionogi Research Site
City
Torrevieja
ZIP/Postal Code
03186
Country
Spain
Facility Name
Shionogi Research Site
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Shionogi Research Site
City
New Taipei City
ZIP/Postal Code
235
Country
Taiwan
Facility Name
Shionogi Research Site
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
Shionogi Research Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Shionogi Research Site
City
Taipei
ZIP/Postal Code
11696
Country
Taiwan
Facility Name
Shionogi Research Site
City
Chernivtsi
ZIP/Postal Code
58001
Country
Ukraine
Facility Name
Shionogi Research Site
City
Dnipropetrovsk
ZIP/Postal Code
49000
Country
Ukraine
Facility Name
Shionogi Research Site
City
Ivano Frankivsk
ZIP/Postal Code
76008
Country
Ukraine
Facility Name
Shionogi Research Site
City
Kharkiv
ZIP/Postal Code
61037
Country
Ukraine
Facility Name
Shionogi Research Site
City
Kharkiv
ZIP/Postal Code
61103
Country
Ukraine
Facility Name
Shionogi Research Site
City
Kherson
ZIP/Postal Code
73000
Country
Ukraine
Facility Name
Shionogi Research Site
City
Kiev
ZIP/Postal Code
01133
Country
Ukraine
Facility Name
Shionogi Research Site
City
Kiev
ZIP/Postal Code
041112
Country
Ukraine
Facility Name
Shionogi Research Site
City
Kremenchuk
ZIP/Postal Code
39617
Country
Ukraine
Facility Name
Shionogi Research Site
City
Poltava
ZIP/Postal Code
36038
Country
Ukraine
Facility Name
Shionogi Research Site
City
Sumy
ZIP/Postal Code
40031
Country
Ukraine
Facility Name
Shionogi Research Site
City
Vinnitsya
ZIP/Postal Code
21029
Country
Ukraine
Facility Name
Shionogi Research Site
City
Zaporizhzhya
ZIP/Postal Code
69035
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35076335
Citation
Nordmann P, Shields RK, Doi Y, Takemura M, Echols R, Matsunaga Y, Yamano Y. Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials. Microb Drug Resist. 2022 Apr;28(4):398-407. doi: 10.1089/mdr.2021.0180. Epub 2022 Jan 24.
Results Reference
derived
PubMed Identifier
35025025
Citation
Skaar EP, Echols R, Matsunaga Y, Menon A, Portsmouth S. Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study. Eur J Clin Microbiol Infect Dis. 2022 Mar;41(3):467-476. doi: 10.1007/s10096-021-04399-9. Epub 2022 Jan 13.
Results Reference
derived
PubMed Identifier
34792787
Citation
Wenzler E, Butler D, Tan X, Katsube T, Wajima T. Pharmacokinetics, Pharmacodynamics, and Dose Optimization of Cefiderocol during Continuous Renal Replacement Therapy. Clin Pharmacokinet. 2022 Apr;61(4):539-552. doi: 10.1007/s40262-021-01086-y. Epub 2021 Nov 18. Erratum In: Clin Pharmacokinet. 2022 Jul;61(7):1069.
Results Reference
derived
PubMed Identifier
33058798
Citation
Wunderink RG, Matsunaga Y, Ariyasu M, Clevenbergh P, Echols R, Kaye KS, Kollef M, Menon A, Pogue JM, Shorr AF, Timsit JF, Zeitlinger M, Nagata TD. Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2021 Feb;21(2):213-225. doi: 10.1016/S1473-3099(20)30731-3. Epub 2020 Oct 12.
Results Reference
derived

Learn more about this trial

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

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