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Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia

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ClinicalTrials.gov Identifier: NCT03138733
Recruitment Status : Completed
First Posted : May 3, 2017
Results First Posted : May 6, 2023
Last Update Posted : November 8, 2023
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Basilea Pharmaceutica

Study Description
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Brief Summary:
The purpose of this study was to compare the efficacy and safety of ceftobiprole medocaril versus a comparator in the treatment of patients with complicated Staphylococcus aureus bacteremia (SAB).

Condition or disease Intervention/treatment Phase
Staphylococcus Aureus Bacteremia Drug: Ceftobiprole medocaril Drug: Daptomycin Phase 3

Detailed Description:

Patients were randomized 1:1 to ceftobiprole or the comparator regimen. Randomization was stratified by study site, dialysis status, and prior antibacterial treatment use within 7 days before randomization.

The three phases of the study were:

  1. Screening assessments of up to 72 hours prior to randomization
  2. Randomization and subsequent active treatment with intravenous (i.v.) study drug (ceftobiprole or daptomycin ± aztreonam).
  3. Post-treatment, comprising an end of trial (EOT) visit (within 72 hours of last study-drug administration), Day 35 (± 3 days), Day 42 (± 3 days), and a post-treatment evaluation (PTE) visit on Day 70 (± 5 days) post-randomization.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 390 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Multi-center Study to Establish the Efficacy and Safety of Ceftobiprole Medocaril Compared to Daptomycin in the Treatment of Staphylococcus Aureus Bacteremia, Including Infective Endocarditis
Actual Study Start Date : August 26, 2018
Actual Primary Completion Date : March 11, 2022
Actual Study Completion Date : March 11, 2022

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Ceftobiprole medocaril
Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril)
 Drug: Ceftobiprole medocaril
Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril) as a 2 h infusion
Active Comparator: Daptomycin
Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards), with or without aztreonam
 Drug: Daptomycin
Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards) as a 0.5 h infusion, with or without aztreonam


Outcome Measures
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Primary Outcome Measures :
  1. Number of Patients With or Without Overall Success at the Post-treatment Evaluation (PTE) Visit [ Time Frame: PTE visit on Day 70 (± 5 days) post-randomization ]

    Comparison of overall success rates in the mITT population

    Overall success at PTE for the mITT population was defined as all of the following criteria being met (Responder):

    1. Patient alive at Day 70 (± 5 days) post-randomization.
    2. No new metastatic foci or complications of the SAB infection.
    3. Resolution or improvement of SAB-related clinical signs and symptoms.
    4. Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)


Secondary Outcome Measures :
  1. Number of Patients With or Without Overall Success at the PTE Visit in the CE Population [ Time Frame: At PTE visit on Day 70 (± 5 days) post-randomization ]

    Comparison of overall success rates in the Clinical Evaluable (CE) population

    Overall success at PTE for the CE population was defined as all of the following criteria being met (Responder):

    1. Patient alive at Day 70 (± 5 days) post-randomization.
    2. No new metastatic foci or complications of the SAB infection.
    3. Resolution or improvement of SAB-related clinical signs and symptoms.
    4. Two negative blood cultures for S. aureus (without any subsequent positive blood culture for S. aureus)

  2. Number of Patients With Microbiological Eradication at the PTE Visit [ Time Frame: At PTE visit on Day 70 (± 5 days) post-randomization ]
    Comparison of microbiological eradication rates in the mITT population. Microbiological eradication rate was defined as a negative blood culture for S. aureus during study treatment and another negative blood culture during the follow up period up to PTE.

  3. All-cause Mortality at the PTE Visit [ Time Frame: At PTE visit on Day 70 (± 5 days) post-randomization ]
    Comparison of all-cause mortality rates in the mITT population

  4. Number of Patients With or Without New Metastatic Foci or Other Complications of SAB Developed After Day 7 [ Time Frame: Assessment after Day 7 post-randomization through to post-treatment evaluation (PTE) visit on Day 70 (± 5 days) ]
    Comparison of complication rates in the mITT population defined by number of patients with development of new metastatic foci or other complications of SAB after Day 7

  5. Time to Staphylococcus Aureus Bloodstream Clearance [ Time Frame: Up to 6 weeks post-randomization ]
    Time-to-event in the mITT Bloodstream clearance was defined as two consecutive study days with blood-culture-negative assessments for S. aureus, without any subsequent S. aureus relapse or reinfection

  6. Number of Patients With or Without Adverse Events (AEs) [ Time Frame: AEs were assessed from the first dose of study drug through the post-treatment evaluation (PTE) visit on Day 70 (± 5 days) ]
    Treatment-emergent adverse events in the safety population


Eligibility Criteria
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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:

  • Male or female ≥ 18 years of age
  • Staphylococcus aureus bacteremia (SAB), based on at least one positive blood culture obtained within the 72 h prior to randomization

  • At least one of the following signs or symptoms of bacteremia:

    1. fever (e.g.≥ 38 °C/100.4 °F measured orally)
    2. white blood cell count > 10,000 or < 4,000 cells/µL, or > 10% immature neutrophils (bands)
    3. tachycardia (heart rate > 90 bpm)
    4. hypotension (systolic blood pressure < 90 mmHg)

  • At least one of the following:

    1. SAB in patients undergoing chronic intermittent hemodialysis or peritoneal dialysis
    2. Persistent SAB
    3. Definite native-valve right-sided infective endocarditis by Modified Duke's Criteria
    4. Other forms of complicated SAB
    5. Osteomyelitis (including vertebral, sternal, or long-bone osteomyelitis)
    6. Epidural or cerebral abscess
  • Other inclusion criteria have been applied

Exclusion Criteria:

  • Treatment with potentially effective (anti-staphylococcal) systemic antibacterial treatment for more than 48 h within the 7 days prior to randomization; Exception: Documented failure of bloodstream clearance
  • Bloodstream or non-bloodstream concomitant infections with Gram-negative bacteria that are known to be non-susceptible to either ceftobiprole or aztreonam
  • Left-sided infective endocarditis
  • Prosthetic cardiac valves or valve support rings, cardiac pacemakers, automatic implantable cardioverter-defibrillator, or left-ventricular assist devices
  • Community- or hospital-acquired pneumonia
  • Opportunistic infections within 30 days prior to randomization, where the underlying cause of these infections is still active
  • Requirement for continuous renal-replacement therapy
  • Women who are pregnant or nursing
  • Other exclusion criteria have been applied
Contacts and Locations
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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): NCT03138733


Locations
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Sponsors and Collaborators
Basilea Pharmaceutica
Department of Health and Human Services
Investigators
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Study Director: Marc Engelhardt, MD Basilea Pharmaceutica
  Study Documents (Full-Text)

Documents provided by Basilea Pharmaceutica:
Study Protocol  [PDF] February 27, 2020
Statistical Analysis Plan  [PDF] June 17, 2022

More Information
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Publications of Results:

Other Publications:

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Responsible Party: Basilea Pharmaceutica
ClinicalTrials.gov Identifier: NCT03138733    
Other Study ID Numbers: BPR-CS-009
First Posted: May 3, 2017    Key Record Dates
Results First Posted: May 6, 2023
Last Update Posted: November 8, 2023
Last Verified: October 2023
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 Basilea Pharmaceutica:
Ceftobiprole, daptomycin, Staphylococcus aureus
Bacteremia, bloodstream infection
Additional relevant MeSH terms:
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Staphylococcal Infections
Bacteremia
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Sepsis
Systemic Inflammatory Response Syndrome
 Inflammation
Pathologic Processes
Daptomycin
Ceftobiprole
Ceftobiprole medocaril
Anti-Bacterial Agents
Anti-Infective Agents