Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

Basilea Pharmaceutica

Status and phase: Completed; Phase 3

Conditions: Hospital-acquired Pneumonia (HAP); Community-acquired Pneumonia (CAP)

Treatments: Drug: ceftobiprole medocaril; Drug: IV standard-of-care cephalosporin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03439124

BPR-PIP-002

Details and patient eligibility

About

This was a study of the safety and efficacy of ceftobiprole medocaril compared with intravenous (IV) standard-of-care cephalosporin treatment with or without vancomycin in pediatric patients with either hospital-acquired bacterial pneumonia (HAP) or community-acquired bacterial pneumonia (CAP) requiring hospitalization, and requiring intravenous (IV) antibiotic therapy.

Full description

This was a randomized, investigator-blind, active-controlled multi-center study to evaluate the safety, tolerability, pharmacokinetics and efficacy of ceftobiprole medocaril compared with IV standard-of-care cephalosporin treatment with or without vancomycin in pediatric patients aged 3 months to less than 18 years with HAP or CAP requiring hospitalization and therapy with IV antibiotics. Randomization was stratified by four age groups (3 months to < 2 years; 2 years to < 6 years; 6 years to < 12 years; 12 years to < 18 years), and by diagnosis of HAP or CAP.

Enrollment: 138 patients

Sex: All

Ages: 3 months to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male of female aged 3 months to < 18 years with a body weight of at least 5 kg
• Diagnosis of either hospital-acquired pneumonia or community-acquired pneumonia requiring hospitalization and administration of IV antibiotic therapy
• New or progressive imaging findings consistent with bacterial pneumonia
• Requirement for IV antibacterial treatment for pneumonia
• Other inclusion criteria may apply

Exclusion criteria

• Known resistance of the causative pathogen to ceftobiprole or IV standard-of-care cephalosporin treatment (± vancomycin)
• On mechanical ventilation
• Chest trauma with severe lung contusion or flail chest
• Acute respiratory distress syndrome
• Empyema or lung abscess
• Anatomical bronchial obstruction
• Active or currently treated pulmonary tuberculosis
• Atypical bacterial pneumonia, or viral pneumonia without bacterial superinfection, or need for antibiotic coverage with a macrolide
• Pertussis, chemical pneumonitis, or cystic fibrosis
• Severe immunodeficiency
• Significant laboratory abnormalities including: Hematocrit <20%; absolute neutrophil count <0.5x10⁹/L; platelet count <50x10⁹/L; alanine aminotransferase, aspartate aminotransferase, or bilirubin >5 times the age-specific upper limit of normal;
• Creatinine clearance <50 mL/min/1.73 m²
• Use of systemic antimicrobial therapy for more than 24 hours in the 48 hours before randomization
• History of a previous clinically-relevant hypersensitivity or serious adverse reaction to beta lactam antibiotics or to vancomycin
• Poorly controlled seizure disorder
• Other exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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138 participants in 2 patient groups

Ceftobiprole medocaril

Experimental group

Description:

Ceftobiprole medocaril is the water-soluble prodrug of ceftobiprole, an advanced-generation cephalosporin developed for IV administration. Ceftobiprole is characterized by potent, broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative pathogens.

Treatment:

Drug: ceftobiprole medocaril

IV standard-of-care cephalosporin

Active Comparator group

Description:

Ceftriaxone was used as standard-of-care cephalosporin for the treatment of CAP. It is a third-generation cephalosporin with activity against typical bacterial pathogens of CAP requiring hospitalization, and is widely used for the treatment of various bacterial infections in neonates, infants, children, and adults. Ceftazidime was used as standard-of-care cephalosporin for the treatment of HAP. It is also a third-generation cephalosporin, but with broader activity against Gram-negative aerobic bacilli, including Pseudomonas aeruginosa. Vancomycin is a glycopeptide antibiotic that is active against staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA). At the discretion of the blinded investigator, patients received vancomycin in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.

Treatment:

Drug: IV standard-of-care cephalosporin