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

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ClinicalTrials.gov Identifier: NCT03032380
Recruitment Status : Completed
First Posted : January 26, 2017
Last Update Posted : April 4, 2019
Sponsor:
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )

Brief Summary:
To compare all-cause mortality at Day 14 in participants receiving S-649266 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.

Condition or disease Intervention/treatment Phase
Healthcare-associated Pneumonia (HCAP) Hospital Acquired Pneumonia (HAP) Ventilator Associated Pneumonia (VAP) Drug: S-649266 Drug: Meropenem Drug: Linezolid Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : October 24, 2017
Actual Primary Completion Date : February 26, 2019
Actual Study Completion Date : April 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: S-649266
Participants will receive 2 g S-649266 administered intravenously every 8 hours for 7 to 14 days and 600 mg linezolid administered intravenously every 12 hours for at least 5 days.
Drug: S-649266
2000 mg intravenously every 8 hours for a period of 7 to14 days (dosage adjustment is necessary based on renal function)
Other Name: Cefiderocol

Drug: Linezolid
600 mg of Linezolid will be administered intravenously over 30 minutes to 2 hours, every 12 hours.
Other Name: Zyvox®

Active Comparator: Meropenem
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.
Drug: Meropenem
2000 mg intravenously every 8 hours for a period of 7 to 14 days (dosage adjustment is necessary based on renal function)
Other Name: Merrem®

Drug: Linezolid
600 mg of Linezolid will be administered intravenously over 30 minutes to 2 hours, every 12 hours.
Other Name: Zyvox®




Primary Outcome Measures :
  1. All-cause Mortality at Day 14 [ Time Frame: Day 14 ]
    The mortality from all-causes in each arm of the study by the fourteenth day after the start of treatment.


Secondary Outcome Measures :
  1. Percentage of Participants with a Clinical Outcome of Clinical Cure at Test of Cure (TOC) [ Time Frame: Test of cure, defined as 7 days after end of treatment (treatment duration is 7-14 days) ]
    Clinical outcome will be assessed by the investigator as either: clinical cure, clinical failure, or indeterminate.

  2. Percentage of Participants with a Microbiologic Outcome of Eradication at TOC [ Time Frame: Test of cure, defined as 7 days after end of treatment (treatment duration is 7-14 days) ]
    The microbiological outcome by baseline pathogen at TOC will be determined by the sponsor as either: eradication, persistence, or indeterminate.

  3. Percentage of Participants with a Clinical Outcome of Clinical Cure at Early Assessment (EA) [ Time Frame: Early assessment, defined as 3-4 days after the start of treatment. ]
    Clinical outcome at EA will be assessed as either: clinical cure, clinical failure, or indeterminate.

  4. Percentage of Participants with a Clinical Outcome of Clinical Cure at End of Treatment (EOT) [ Time Frame: End of treatment, defined as the last day of study treatment (7-14 days) ]
    Clinical outcome will be assessed by the investigator at EOT as either: clinical cure, clinical failure, or indeterminate.

  5. Percentage of Participants with a Clinical Outcome of Sustained Clinical Cure at Follow-up (FU) [ Time Frame: Follow-up, defined as 14 days after the end of treatment (treatment duration is 7-14 days) ]
    Clinical outcome will be assessed by the investigator at FU as either: Sustained clinical cure, relapse, or indeterminate.

  6. Percentage of Participants with a Microbiologic Outcome of Eradication at EA [ Time Frame: Early assessment, defined as 3-4 days after the start of treatment. ]
    The microbiological outcome by baseline pathogen will be determined by the sponsor at EA as either: eradication, persistence, or indeterminate.

  7. Percentage of Participants with a Microbiologic Outcome of Eradication at EOT [ Time Frame: End of treatment, defined as the last day of study treatment (7-14 days) ]
    The microbiological outcome by baseline pathogen will be determined by the sponsor at EOT as either: eradication, persistence or indeterminate.

  8. Percentage of Participants with a Microbiologic Outcome of Sustained Eradication at FU [ Time Frame: Follow-up, defined as 14 days after the end of treatment (treatment duration is 7-14 days) ]
    Microbiological outcome by baseline pathogen will be determined by the sponsor at FU as either: Sustained eradication, recurrence, or indeterminate.

  9. All-cause Mortality at Day 28 [ Time Frame: Day 28 ]
    The mortality from all-causes in each arm of the study by the twenty-eighth day after the start of treatment.

  10. All-cause Mortality Over the Full Duration of the Study [ Time Frame: From start of treatment through study completion (up to 42 days) ]
    The mortality from all-causes in each arm of the study for the full duration of the study.

  11. Number of 24-hour Days Associated with the Treatment of the Infection [ Time Frame: Treatment period (7-14 days) ]
    Resource utilization

  12. Number of Participants with Adverse Events [ Time Frame: From baseline through study completion (up to 42 days) ]
    Incidence and severity of adverse events in each arm of the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03032380


  Show 119 Study Locations
Sponsors and Collaborators
Shionogi
Investigators
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Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi

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Responsible Party: Shionogi
ClinicalTrials.gov Identifier: NCT03032380     History of Changes
Other Study ID Numbers: 1615R2132
2016-003020-23 ( EudraCT Number )
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: April 4, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shionogi Inc. ( Shionogi ):
Hospital-acquired pneumonia (HAP)
S-649266
linezolid
meropenem
Healthcare-associated pneumonia (HCAP)
nosocomial pneumonia
Ventilator-associated pneumonia (VAP)
Gram-negative pathogens
pneumonia
cefiderocol

Additional relevant MeSH terms:
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Pneumonia
Pneumonia, Ventilator-Associated
Healthcare-Associated Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Iatrogenic Disease
Disease Attributes
Pathologic Processes
Linezolid
Meropenem
Cephalosporins
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action