Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia

Basilea Pharmaceutica

Status and phase: Completed; Phase 3

Conditions: Staphylococcus Aureus Bacteremia

Treatments: Drug: Ceftobiprole medocaril; Drug: Daptomycin

Study type: Interventional

Funder types: Industry; Other U.S. Federal agency

Identifiers

NCT03138733

BPR-CS-009

Details and patient eligibility

About

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).

Full 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.

Enrollment: 390 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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390 participants in 2 patient groups

Ceftobiprole medocaril

Experimental group

Description:

Ceftobiprole 500 mg (as 667 mg ceftobiprole medocaril)

Treatment:

Drug: Ceftobiprole medocaril

Daptomycin

Active Comparator group

Description:

Daptomycin 6 mg/kg (up to 10 mg/kg based on institutional standards), with or without aztreonam

Treatment:

Drug: Daptomycin