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Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens (CREDIBLE - CR)

Primary Purpose

Healthcare-associated Pneumonia (HCAP), Bloodstream Infections (BSI), Hospital Acquired Pneumonia (HAP)

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Cefiderocol

Best Available Therapy

About this trial

This is an interventional treatment trial for Healthcare-associated Pneumonia (HCAP) focused on measuring cefiderocol, Bloodstream infections (BSI), Complicated urinary tract infection (cUTI), Ventilator associated pneumonia (VAP), Hospital acquired pneumonia (HAP), Sepsis, multi-drug resistant pathogens, S-649266, Gram-negative pathogens, Healthcare-associated pneumonia (HCAP), carbapenem resistant pathogens

Eligibility Criteria

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

Inclusion Criteria:

Patients with clinically documented infection (HAP/VAP/HCAP, cUTI, or BSI/sepsis) caused by a Gram-negative pathogen with evidence of carbapenem resistance
Patients who have been treated previously with an empiric antibiotic regiment and failed treatment, both clinically and microbiologically, are eligible for the study, if they have an identified carbapenem-resistant Gram-negative pathogen which has either been shown to be nonsusceptible in vitro to each of the antibiotic(s) of the empiric antibiotic regimen or been grown from a culture performed after at least 2 days of the empiric antibiotic regimen
Patient is male (no contraception required) or female and meets one of the following criteria:
- Surgically sterile by hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy or tubal ligation for the purpose of contraception for at least 6 weeks with appropriate documentation of such surgery
- Postmenopausal (defined as older than 45 years of age with cessation of regular menstrual periods for 6 months and confirmed by a follicle-stimulating hormone level of > 40 mIU/mL, or amenorrhea for at least 12 months)
- Of childbearing potential and using combined (estrogen and progestogen) or progestogen-only hormonal contraception associated with inhibition of ovulation (including oral, intravaginal, injectable, implantable, and transdermal contraceptives), or an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS) for the entire duration of the study
- Of childbearing potential and practice abstinence as a preferred and usual lifestyle, and agrees to continue practicing abstinence from Screening and for the entire duration of the study
- Of childbearing potential, whose sole heterosexual partner has been successfully vasectomized and agrees to not have other heterosexual partners for the entire duration of the study
Patients meeting specific criteria for each infection site

Exclusion Criteria:

Patients who have a history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment)
Patients who need more than 3 systemic antibiotics as part of best available therapy (BAT) for the treatment of the Gram-negative infection (patients with mixed Gram-positive or anaerobic infections may receive appropriate concomitant narrow spectrum antibiotics [eg, vancomycin, linezolid, metronidazole, clindamycin])
Patients with coinfection caused by invasive aspergillosis, mucormycosis or other highly lethal mold
Patients who have central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection)
Patients with infection requiring > 3 weeks of antibiotic treatment (eg, bone and joint infection, endocarditis)
Patients with cystic fibrosis or moderate to severe bronchiectasis
Patients in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at the time of Randomization
Patients with severe neutropenia, ie, polymorphonuclear neutrophils (PMNs) < 100 cells/μL
Female patients who have a positive pregnancy test at Screening or who are lactating
Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30
Patients who have received a potentially effective antibiotic regimen for the carbapenem-resistant Gram-negative infection for a continuous duration of more than 24 hours in cUTI, or 36 hours in HAP/VAP/HCAP or BSI/sepsis during the 72 hours leading to Randomization
Patients with any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the study data
Patients who have received another investigational drug or device within 30 days prior to study entry
Patients who have previously been randomized in this study or received S-649266
Patients receiving peritoneal dialysis
Patients meeting specific exclusion criteria for each infection site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cefiderocol

Best Available Therapy (BAT)

Arm Description

Participants will receive cefiderocol 2 g administered intravenously over 3 hours, every 8 hours for 7-14 days. Treatment could be extended to 21 days at the discretion of the investigator.

Best available therapy (BAT) will be chosen by the investigator and may include up to three antibacterial agents for carbapenem resistant Gram-negative bacteria, intravenously administered per country-specific guidelines for 7-14 days. Treatment could be extended to 21 days at the discretion of the investigator.

Outcomes

Primary Outcome Measures

Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Clinical cure was defined as resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. Participants with missing data were considered as non-responders.

Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI

Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ colony-forming units (CFU)/mL was reduced to < 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.

Secondary Outcome Measures

Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis

Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: 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. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy was required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC.

Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.

Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI

Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.

Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.

Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy is required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy is required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.

Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis: HAP/VAP/HCAP: Resolution or substantial improvement of Baseline signs and symptoms of pneumonia including a reduction in SOFA and CPIS scores, and improvement or lack of progression of chest radiographic abnormalities such that no antibacterial therapy was required for the treatment of the current infection. BSI/Sepsis: Resolution or substantial improvement of Baseline signs and symptoms including a reduction in SOFA score, such that no antibacterial therapy was required for the treatment of BSI/sepsis. Participants with bacteremia must have eradication of bacteremia caused by the Gram-negative pathogen. cUTI: Resolution or substantial improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, such that no antibacterial therapy is required for the treatment of the current infection.

Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen

Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen

Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen

Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen

Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen

Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis

Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria established for each infection site: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen 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 to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.

Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. If an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For sepsis, if the participant has a successful clinical outcome after TOC and an appropriate clinical culture could not be obtained, the response was presumed sustained eradication. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI

Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to < 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI

Microbiological outcome per Baseline pathogen at follow-up was determined by the sponsor as defined for each infection site. For cUTI sustained eradication was defined as a culture taken any time after documented eradication at TOC and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained <10³ CFU/mL. Overall per-participant sustained eradication was defined as sustained eradication of all Baseline Gram-negative pathogens.

Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Microbiological outcomes per Baseline pathogen were determined by the sponsor according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to < 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.

Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained < 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen

Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained < 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen

Microbiological outcome per Baseline carbapenem-resistant pathogen were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen. If it was not possible to obtain an appropriate clinical culture and the participant had a successful clinical outcome, the response was presumed to be eradication. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture and/or other primary source as applicable. In the case of sepsis, if the participant had a successful clinical outcome and it was not possible to obtain an appropriate clinical culture, the response was presumed to be eradication. cUTI: a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to < 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.

Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained < 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia

The percentage of participants who experienced eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture.

Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia

The percentage of participants who experienced sustained eradication of the Baseline documented carbapenem-resistant Gram-negative bacteremia, defined as absence of the Baseline Gram-negative pathogen from a blood culture after TOC.

Percentage of Participants With a Composite Clinical and Microbiological Response at EOT

The composite clinical and microbiological response rate is defined as the percentage of participants with both clinical cure and microbiologic eradication, as defined above for each site of infection.

Percentage of Participants With a Composite Clinical and Microbiological Response at TOC

Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up

The composite clinical and microbiological response rate is defined as the percentage of participants with both sustained clinical cure and sustained microbiologic eradication, as defined above for each site of infection.

All-cause Mortality at Day 14 and Day 28

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants who experienced mortality regardless of the cause at or before Day 14 and Day 28, respectively.

Percentage of Participants Alive and With No Change in Antibiotic Treatment Due to Either Lack of Therapeutic Benefit or Drug-related Toxicity at TOC

Survival Time

Survival time was analyzed by Kaplan-Meier survival curve. The table below presents deaths that occurred in10-day time intervals through the end of study

Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP)

Clinical pulmonary infection score (CPIS) is a surrogate for diagnosis and treatment response. Points (0, 1, or 2) are assigned for observed findings for 5 variables including body temperature, white blood cell count, tracheal secretions, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), and chest radiograph infiltrates. The total score ranges from 0 to 10, where higher scores may indicate a higher likelihood of mortality; a negative change from Baseline indicates improvement

Change From Baseline in Sequential Organ Failure Assessment (SOFA)

The SOFA score is a scoring system to determine the extent of a patient's organ function or rate of failure. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each score is from 0 to 4, and the total score ranges from 0 to 24, where higher scores indicate a higher likelihood of mortality. A negative change from Baseline score indicates improvement.

Number of Participants With Adverse Events

The severity of each adverse event (AE) was graded by the investigator according to the following definitions: Mild: Symptom or finding 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 interruption of usual daily activities or has a clinically significant effect The relationship of AEs to study treatment was determined by the investigator according to the following definition: ● Related: An AE which can be reasonably explained as having been caused by the study treatment. A serious AE is defined as any AE that resulted in any of the following outcomes: Death Life-threatening condition Hospitalization or prolongation of existing hospitalization Persistent or significant disability/incapacity Congenital anomaly/birth defect Other medically important condition

Full Information

NCT ID

NCT02714595

First Posted

February 26, 2016

Last Updated

December 18, 2020

Sponsor

Shionogi

1. Study Identification

Unique Protocol Identification Number

NCT02714595

Brief Title

Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

Acronym

CREDIBLE - CR

Official Title

A Multicenter, Randomized, Open-label Clinical Study of S-649266 or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

September 7, 2016 (Actual)

Primary Completion Date

April 1, 2019 (Actual)

Study Completion Date

April 22, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shionogi

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study is designed to provide evidence of efficacy of cefiderocol in the treatment of serious infections in adult patients caused by carbapenem-resistant Gram-negative pathogens.

Detailed Description

This study is designed to provide evidence of efficacy of cefiderocol in the treatment of serious infections in adult patients with either hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), healthcare-associated pneumonia (HCAP), complicated urinary tract infection (cUTI), or bloodstream infections (BSI)/sepsis caused by carbapenem-resistant 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), Bloodstream Infections (BSI), Hospital Acquired Pneumonia (HAP), Complicated Urinary Tract Infection (cUTI), Sepsis, Ventilator Associated Pneumonia (VAP)

Keywords

cefiderocol, Bloodstream infections (BSI), Complicated urinary tract infection (cUTI), Ventilator associated pneumonia (VAP), Hospital acquired pneumonia (HAP), Sepsis, multi-drug resistant pathogens, S-649266, Gram-negative pathogens, Healthcare-associated pneumonia (HCAP), carbapenem resistant pathogens

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

152 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cefiderocol

Arm Type

Experimental

Arm Description

Participants will receive cefiderocol 2 g administered intravenously over 3 hours, every 8 hours for 7-14 days. Treatment could be extended to 21 days at the discretion of the investigator.

Arm Title

Best Available Therapy (BAT)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cefiderocol

Other Intervention Name(s)

S-649266, Fetroja ®

Intervention Description

2 g intravenously over 3 hours every 8 hours for a period of 7 to 14 days, or 2 g every 6 hours for participants with creatinine clearance >120 mL/min.

Intervention Type

Drug

Intervention Name(s)

Best Available Therapy

Intervention Description

Standard of care with either a polymyxin-based or non-polymyxin-based regimen as determined by the investigator and consisting of one to three marketed antibacterial agent(s).

Primary Outcome Measure Information:

Title

Percentage of Participants With Clinical Cure at Test of Cure (TOC) in Participants With HAP/VAP/HCAP or BSI/Sepsis

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Microbiologic Eradication at TOC in Participants With cUTI

Description

Time Frame

Test of cure, defined as 7 days after the end of treatment, equivalent to Study Days 14 to 21

Secondary Outcome Measure Information:

Title

Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With HAP/VAP/HCAP or BSI/Sepsis

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Sustained Clinical Cure at Follow-up (FU) in Participants With HAP/VAP/HCAP or BSI/Sepsis

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Clinical Cure at Test of Cure in Participants With cUTI

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Clinical Cure at End of Treatment (EOT) in Participants With cUTI

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With cUTI

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Clinical Cure at End of Treatment in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Clinical Cure at Test of Cure in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Clinical Cure at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Description

Clinical response was based on the investigator's evaluation of the participant's clinical signs and symptoms and was defined for each diagnosis. Sustained clinical cure for HAP/VAP/HCAP: Continued resolution or substantial improvement of Baseline signs and symptoms of pneumonia, such that no antibacterial therapy is required for the treatment of pneumonia in a participant assessed as cured at TOC. BSI/Sepsis: Continued resolution or substantial improvement of Baseline signs and symptoms associated with reduction in SOFA score, such that no antibacterial therapy is required for the treatment of the original BSI/sepsis in a participant assessed as cured at TOC. cUTI: Continued resolution or improvement of Baseline signs and symptoms of cUTI, or return to pre-infection Baseline if known, in a participant assessed as cured at TOC.

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Clinical Cure at End of Treatment By Baseline Pathogen

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Clinical Cure at Test of Cure By Baseline Pathogen

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Pathogen

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Clinical Cure at EOT By Baseline Carbapenem-resistant Pathogen

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Clinical Cure at TOC By Baseline Carbapenem-resistant Pathogen

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Clinical Cure at Follow-up By Baseline Carbapenem-resistant Pathogen

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP or BSI/Sepsis

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP or BSI/Sepsis

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP or BSI/Sepsis

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Microbiologic Eradication at EOT in Participants With cUTI

Description

Microbiological outcome per Baseline pathogen was determined by the sponsor as defined for each infection site. For cUTI eradication was defined as a urine culture that showed that the Gram-negative uropathogen identified at Baseline at ≥ 10⁵ CFU/mL was reduced to < 10³ CFU/mL. Overall per-participant eradication was defined as eradication of all Baseline Gram-negative pathogens.

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With cUTI

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Microbiologic Eradication at EOT in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Microbiologic Eradication at TOC in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With HAP/VAP/HCAP + BSI/Sepsis, and Overall

Description

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained < 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Microbiologic Eradication at EOT By Baseline Pathogen

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Microbiologic Eradication at TOC By Baseline Pathogen

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Pathogen

Description

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained < 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Microbiologic Eradication at EOT By Baseline Carbapenem-resistant Pathogen

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Microbiologic Eradication at TOC By Baseline Carbapenem-resistant Pathogen

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up By Baseline Carbapenem-resistant Pathogen

Description

Microbiological outcomes per Baseline pathogen at FU were determined according to the following criteria for each diagnosis: HAP/VAP/HCAP: Sustained eradication was defined as the absence of the Baseline Gram-negative pathogen from an appropriate clinical specimen after TOC. BSI/Sepsis: Absence of the Baseline Gram-negative pathogen from a blood culture or other primary source after TOC as applicable. For HAP/VAP/HCAP and sepsis if an appropriate clinical culture could not be obtained and the participant had a successful clinical response after TOC, the response was presumed sustained eradication. cUTI: a culture taken any time after documented eradication at TOC, and a urine culture obtained at FU showed that the Baseline uropathogen found at entry at ≥10⁵ CFU/mL remained < 10³ CFU/mL. Overall per-participant response was defined as sustained eradication of all Baseline Gram-negative pathogens after documented eradication at TOC.

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With Microbiologic Eradication at EOT in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With Microbiologic Eradication at TOC in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With Sustained Microbiologic Eradication at Follow-up in Participants With Documented Carbapenem-resistant Gram-negative Bacteremia

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

Percentage of Participants With a Composite Clinical and Microbiological Response at EOT

Description

Time Frame

End of treatment, Day 7 to 14

Title

Percentage of Participants With a Composite Clinical and Microbiological Response at TOC

Description

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Percentage of Participants With a Composite Clinical and Microbiological Response at Follow-up

Description

Time Frame

Follow-up, defined as 14 days after the end of treatment, equivalent to Study Day 21 to 28

Title

All-cause Mortality at Day 14 and Day 28

Description

The all-cause mortality rate at Day 14 and Day 28 was calculated as the percentage of participants who experienced mortality regardless of the cause at or before Day 14 and Day 28, respectively.

Time Frame

Day 14 and Day 28

Title

Percentage of Participants Alive and With No Change in Antibiotic Treatment Due to Either Lack of Therapeutic Benefit or Drug-related Toxicity at TOC

Time Frame

Test of cure, defined as 7 days after end of treatment, equivalent to Study Day 14 to 21

Title

Survival Time

Description

Survival time was analyzed by Kaplan-Meier survival curve. The table below presents deaths that occurred in10-day time intervals through the end of study

Time Frame

Days 1 to 10, 11 to 20, 21 to 30, 31 to 40, 41-50, and 51 to 60.

Title

Change From Baseline in Clinical Pulmonary Infection Score (CPIS) in Participants With Pneumonia (HAP/VAP/HCAP)

Description

Time Frame

Baseline, end of treatment (Day 7-14), test of cure (7 days after end of treatment, equivalent to Study Day 14 to 21) and follow-up (14 days after end of treatment, equivalent to Study Day 21 to 28)

Title

Change From Baseline in Sequential Organ Failure Assessment (SOFA)

Description

Time Frame

Baseline, end of treatment (Day 7 to 14), test of cure (7 days after end of treatment, equivalent to Study Day 14 to 21) and follow-up (14 days after end of treatment, equivalent to Study Day 21 to 28)

Title

Number of Participants With Adverse Events

Description

Time Frame

From first dose of study drug up to 28 days after last dose; maximum treatment duration was 29 days in the cefiderocol group and 22 days in the BAT group.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with clinically documented infection (HAP/VAP/HCAP, cUTI, or BSI/sepsis) caused by a Gram-negative pathogen with evidence of carbapenem resistance Patients who have been treated previously with an empiric antibiotic regiment and failed treatment, both clinically and microbiologically, are eligible for the study, if they have an identified carbapenem-resistant Gram-negative pathogen which has either been shown to be nonsusceptible in vitro to each of the antibiotic(s) of the empiric antibiotic regimen or been grown from a culture performed after at least 2 days of the empiric antibiotic regimen Patient is male (no contraception required) or female and meets one of the following criteria: Surgically sterile by hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy or tubal ligation for the purpose of contraception for at least 6 weeks with appropriate documentation of such surgery Postmenopausal (defined as older than 45 years of age with cessation of regular menstrual periods for 6 months and confirmed by a follicle-stimulating hormone level of > 40 mIU/mL, or amenorrhea for at least 12 months) Of childbearing potential and using combined (estrogen and progestogen) or progestogen-only hormonal contraception associated with inhibition of ovulation (including oral, intravaginal, injectable, implantable, and transdermal contraceptives), or an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS) for the entire duration of the study Of childbearing potential and practice abstinence as a preferred and usual lifestyle, and agrees to continue practicing abstinence from Screening and for the entire duration of the study Of childbearing potential, whose sole heterosexual partner has been successfully vasectomized and agrees to not have other heterosexual partners for the entire duration of the study Patients meeting specific criteria for each infection site Exclusion Criteria: Patients who have a history of any moderate or severe hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment) Patients who need more than 3 systemic antibiotics as part of best available therapy (BAT) for the treatment of the Gram-negative infection (patients with mixed Gram-positive or anaerobic infections may receive appropriate concomitant narrow spectrum antibiotics [eg, vancomycin, linezolid, metronidazole, clindamycin]) Patients with coinfection caused by invasive aspergillosis, mucormycosis or other highly lethal mold Patients who have central nervous system (CNS) infection (eg, meningitis, brain abscess, shunt infection) Patients with infection requiring > 3 weeks of antibiotic treatment (eg, bone and joint infection, endocarditis) Patients with cystic fibrosis or moderate to severe bronchiectasis Patients in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at the time of Randomization Patients with severe neutropenia, ie, polymorphonuclear neutrophils (PMNs) < 100 cells/μL Female patients who have a positive pregnancy test at Screening or who are lactating Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30 Patients who have received a potentially effective antibiotic regimen for the carbapenem-resistant Gram-negative infection for a continuous duration of more than 24 hours in cUTI, or 36 hours in HAP/VAP/HCAP or BSI/sepsis during the 72 hours leading to Randomization Patients with any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the study data Patients who have received another investigational drug or device within 30 days prior to study entry Patients who have previously been randomized in this study or received S-649266 Patients receiving peritoneal dialysis Patients meeting specific exclusion criteria for each infection site

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

Hartford

State/Province

Connecticut

ZIP/Postal Code

06102

Country

United States

Facility Name

Shionogi Research Site

City

Newark

State/Province

Delaware

ZIP/Postal Code

19718

Country

United States

Facility Name

Shionogi Research Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Shionogi Research Site

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70121

Country

United States

Facility Name

Shionogi Research Site

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Facility Name

Shionogi Research Site

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

Shionogi Research Site

City

Salvador

State/Province

Bahia

ZIP/Postal Code

41810-011

Country

Brazil

Facility Name

Shionogi Research Site

City

Curitiba

State/Province

Parana

ZIP/Postal Code

80050

Country

Brazil

Facility Name

Shionogi Research Site

City

Passo Fundo

State/Province

RIO Grande DO SUL

ZIP/Postal Code

99010-080

Country

Brazil

Facility Name

Shionogi Research Site

City

Porto Alegre

State/Province

RIO Grande DO SUL

ZIP/Postal Code

90035-074

Country

Brazil

Facility Name

Shionogi Research Site

City

Porto Alegre

State/Province

RIO Grande DO SUL

ZIP/Postal Code

90035-903

Country

Brazil

Facility Name

Shionogi Research Site

City

Santa Maria

State/Province

RIO Grande DO SUL

ZIP/Postal Code

97105-900

Country

Brazil

Facility Name

Shionogi Research Site

City

São José do Rio Preto

State/Province

SAO Paulo

ZIP/Postal Code

15090

Country

Brazil

Facility Name

Shionogi Research Site

City

São Paulo

State/Province

SAO Paulo

ZIP/Postal Code

04378-000

Country

Brazil

Facility Name

Shionogi Research Site

City

Rijeka

State/Province

Primorje-Gorski Kotar

ZIP/Postal Code

51000

Country

Croatia

Facility Name

Shionogi Research Site

City

Split

ZIP/Postal Code

21000

Country

Croatia

Facility Name

Shionogi Research Site

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Shionogi Research Site

City

Paris

State/Province

Ile-de-france

ZIP/Postal Code

75018

Country

France

Facility Name

Shionogi Research Site

City

La Tronche

State/Province

Rhone-alpes

ZIP/Postal Code

38043

Country

France

Facility Name

Shionogi Research Site

City

Heidelberg

State/Province

Baden-wuerttemberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Shionogi Research Site

City

Bonn

State/Province

Nordrhein-westfalen

ZIP/Postal Code

53105

Country

Germany

Facility Name

Shionogi Research Site

City

Berlin

ZIP/Postal Code

12351

Country

Germany

Facility Name

Shionogi Research Site

City

Athens

State/Province

Attica

ZIP/Postal Code

11526

Country

Greece

Facility Name

Shionogi Research Site

City

Athens

State/Province

Attica

ZIP/Postal Code

12462

Country

Greece

Facility Name

Shionogi Research Site

City

Patra

State/Province

Peloponnese

ZIP/Postal Code

26504

Country

Greece

Facility Name

Shionogi Research Site

City

Larisa

State/Province

Thessaly

ZIP/Postal Code

41110

Country

Greece

Facility Name

Shionogi Research Site

City

Larisa

State/Province

Thessaly

ZIP/Postal Code

41221

Country

Greece

Facility Name

Shionogi Research Site

City

Ciudad de Guatemala

Country

Guatemala

Facility Name

Shionogi Research Site

City

Beer-Sheva

State/Province

Beersheba

ZIP/Postal Code

84101

Country

Israel

Facility Name

Shionogi Research Site

City

Be'er Ya'akov

State/Province

Rehoboth

ZIP/Postal Code

70300

Country

Israel

Facility Name

Shionogi Research Site

City

Tel Hashomer

State/Province

Tel Aviv

ZIP/Postal Code

52621

Country

Israel

Facility Name

Shionogi Research Site

City

Tel-Aviv

State/Province

Tel Aviv

ZIP/Postal Code

64239

Country

Israel

Facility Name

Shionogi Research Site

City

Safed

State/Province

Zefat

ZIP/Postal Code

13100

Country

Israel

Facility Name

Shionogi Research Site

City

Hadera

ZIP/Postal Code

38100

Country

Israel

Facility Name

Shionogi Research Site

City

Haifa

ZIP/Postal Code

31048

Country

Israel

Facility Name

Shionogi Research Site

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Facility Name

Shionogi Research Site

City

Holon

ZIP/Postal Code

58100

Country

Israel

Facility Name

Shionogi Research Site

City

Jerusalem

ZIP/Postal Code

91120

Country

Israel

Facility Name

Shionogi Research Site

City

Cisanello

State/Province

Pisa

ZIP/Postal Code

56124

Country

Italy

Facility Name

Shionogi Research Site

City

Milano

ZIP/Postal Code

20122

Country

Italy

Facility Name

Shionogi Research Site

City

Milano

ZIP/Postal Code

20132

Country

Italy

Facility Name

Shionogi Research Site

City

Milano

ZIP/Postal Code

20162

Country

Italy

Facility Name

Shionogi Research Site

City

Modena

ZIP/Postal Code

41124

Country

Italy

Facility Name

Shionogi Research Site

City

Udine

ZIP/Postal Code

33100

Country

Italy

Facility Name

Shionogi Research Site

City

Nagakute

State/Province

Aichi

ZIP/Postal Code

480-1195

Country

Japan

Facility Name

Shionogi Research Site

City

Shinagawa-ku

State/Province

Tokyo

ZIP/Postal Code

142-8999

Country

Japan

Facility Name

Shionogi Research Site

City

Nagasaki

ZIP/Postal Code

852-8501

Country

Japan

Facility Name

Shionogi Research Site

City

Wonju-si

State/Province

Gangwon-Do

ZIP/Postal Code

26426

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Seoul

State/Province

Gwangjin-gu

ZIP/Postal Code

5030

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Daegu

ZIP/Postal Code

41931

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Daegu

ZIP/Postal Code

41944

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Seoul

ZIP/Postal Code

06591

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Seoul

ZIP/Postal Code

06973

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Seoul

ZIP/Postal Code

07441

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

Facility Name

Shionogi Research Site

City

Terrassa

State/Province

Barcelona

ZIP/Postal Code

08035

Country

Spain

Facility Name

Shionogi Research Site

City

Córdoba

State/Province

Cordoba

ZIP/Postal Code

14004

Country

Spain

Facility Name

Shionogi Research Site

City

Lérida

State/Province

Lleida

ZIP/Postal Code

25198

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

08025

Country

Spain

Facility Name

Shionogi Research Site

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Shionogi Research Site

City

Ciudad Real

ZIP/Postal Code

13005

Country

Spain

Facility Name

Shionogi Research Site

City

Gerona

ZIP/Postal Code

17007

Country

Spain

Facility Name

Shionogi Research Site

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Shionogi Research Site

City

Malaga

ZIP/Postal Code

29010

Country

Spain

Facility Name

Shionogi Research Site

City

Sevilla

ZIP/Postal Code

41009

Country

Spain

Facility Name

Shionogi Research Site

City

Valencia

ZIP/Postal Code

46015

Country

Spain

Facility Name

Shionogi Research Site

City

Zaragoza

ZIP/Postal Code

50009

Country

Spain

Facility Name

Shionogi Research Site

City

Taichung

State/Province

ROC

ZIP/Postal Code

40705

Country

Taiwan

Facility Name

Shionogi Research Site

City

Taipei City

State/Province

Taipei

ZIP/Postal Code

10002

Country

Taiwan

Facility Name

Shionogi Research Site

City

Hualien

ZIP/Postal Code

97002

Country

Taiwan

Facility Name

Shionogi Research Site

City

Kaohsiung

ZIP/Postal Code

81362

Country

Taiwan

Facility Name

Shionogi Research Site

City

Taichung

ZIP/Postal Code

40447

Country

Taiwan

Facility Name

Shionogi Research Site

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Facility Name

Shionogi Research Site

City

Muang Nonthaburi

ZIP/Postal Code

11000

Country

Thailand

Facility Name

Shionogi Research Site

City

Muang

ZIP/Postal Code

40002

Country

Thailand

Facility Name

Shionogi Research Site

City

Bornova

State/Province

Izmir

ZIP/Postal Code

35100

Country

Turkey

Facility Name

Shionogi Research Site

City

Ankara

Country

Turkey

Facility Name

Shionogi Research Site

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

Shionogi Research Site

City

Istanbul

ZIP/Postal Code

34214

Country

Turkey

Facility Name

Shionogi Research Site

City

Trabzon

Country

Turkey

Facility Name

Shionogi Research Site

City

London

State/Province

England

ZIP/Postal Code

SE1 7EH

Country

United Kingdom

Facility Name

Shionogi Research Site

City

London

State/Province

England

ZIP/Postal Code

W 120NN

Country

United Kingdom

Facility Name

Shionogi Research Site

City

London

State/Province

England

ZIP/Postal Code

W12 0HS

Country

United Kingdom

Facility Name

Shionogi Research Site

City

London

State/Province

England

Country

United Kingdom

12. IPD Sharing Statement

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

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

33393598

Citation

Naseer S, Weinstein EA, Rubin DB, Suvarna K, Wei X, Higgins K, Goodwin A, Jang SH, Iarikov D, Farley J, Nambiar S. US Food and Drug Administration (FDA): Benefit-Risk Considerations for Cefiderocol (Fetroja(R)). Clin Infect Dis. 2021 Jun 15;72(12):e1103-e1111. doi: 10.1093/cid/ciaa1799.

Results Reference

derived

PubMed Identifier

33058795

Citation

Bassetti M, Echols R, Matsunaga Y, Ariyasu M, Doi Y, Ferrer R, Lodise TP, Naas T, Niki Y, Paterson DL, Portsmouth S, Torre-Cisneros J, Toyoizumi K, Wunderink RG, Nagata TD. Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial. Lancet Infect Dis. 2021 Feb;21(2):226-240. doi: 10.1016/S1473-3099(20)30796-9. Epub 2020 Oct 12.

Results Reference

derived

PubMed Identifier

31819544

Citation

Bassetti M, Ariyasu M, Binkowitz B, Nagata TD, Echols RM, Matsunaga Y, Toyoizumi K, Doi Y. Designing A Pathogen-Focused Study To Address The High Unmet Medical Need Represented By Carbapenem-Resistant Gram-Negative Pathogens - The International, Multicenter, Randomized, Open-Label, Phase 3 CREDIBLE-CR Study. Infect Drug Resist. 2019 Nov 21;12:3607-3623. doi: 10.2147/IDR.S225553. eCollection 2019.

Results Reference

derived

Learn more about this trial

Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

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Study of Cefiderocol (S-649266) or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens (CREDIBLE - CR)

Healthcare-associated Pneumonia (HCAP), Bloodstream Infections (BSI), Hospital Acquired Pneumonia (HAP)

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial