Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

Phase 3

Completed

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

Interventions: Drug: IV standard-of-care cephalosporin
Drug: ceftobiprole medocaril

Brief Summary: 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.

Detailed 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
IV standard-of-care cephalosporin	IV standard-of-care cephalosporin	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.
Ceftobiprole medocaril	ceftobiprole medocaril	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.

Primary Outcome Measures

Name	Time	Method
Adverse Events	Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days	Reported are adverse events (AEs) during the first 3 days of IV therapy and while patients were on IV therapy irrespective of when they switched to oral antibiotic treatment.

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)	At the test-of-cure (TOC) visit	Comparison of clinical cure rates (signs and symptoms of pneumonia normalized or improved such that no further antibiotic therapy was necessary, and stabilization or improvement of chest X-ray findings if these were available) in the ITT population between ceftobiprole and the comparator at the TOC visit.
Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population	At Day 4	Comparison of early clinical response rates in the ITT population between ceftobiprole and the comparator at Day 4.
Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population	At Day 4	Comparison of early clinical response rates in the CE population between ceftobiprole and the comparator at Day 4.
Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population	At the TOC visit	Comparison of clinical cure rates (signs and symptoms of pneumonia normalized or improved such that no further antibiotic therapy was necessary, and stabilization or improvement of chest X-ray findings if these were available) in the CE population between ceftobiprole and the comparator at the TOC visit.

Locations (19): Bekes County Central Hospital
🇭🇺
Gyula, Hungary
Sf. Maria" Children's Emergency Clinical Hospital
🇷🇴
Iaşi, Romania
Fejer County St. Gyorgy University Teaching Hospital
🇭🇺
Szekesfehervar, Hungary
Alessandrescu-Rusescu National Institute for Mother and Child Health
🇷🇴
Bucharest, Romania
Kanizsai Dorottya Hospital
🇭🇺
Nagykanizsa, Hungary
Torokbalint Pulmonology Institute
🇭🇺
Torokbalint, Hungary
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
🇧🇬
Pleven, Bulgaria
Multiprofile Hospital for Active Treatment
🇧🇬
Ruse, Bulgaria
University Multiprofile Hospital for Active Treatment "Sveti Georgi"
🇧🇬
Plovdiv, Bulgaria
University Multiprofile Hospital for Active Treatment "Aleksandrovska"
🇧🇬
Sofia, Bulgaria
Amtel Hospital First Clinical LLC
🇬🇪
Tbilisi, Georgia
LTD High Technology Medical Center University Clinic
🇬🇪
Tbilisi, Georgia
JSC Evex Hospitals 1
🇬🇪
Tbilisi, Georgia
JSC Evex Hospitals 2
🇬🇪
Tbilisi, Georgia
Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic
🇬🇪
Tbilisi, Georgia
Ltd Tbilisi Pediatric Private Clinic
🇬🇪
Tbilisi, Georgia
Principal SMO Ltd.
🇭🇺
Baja, Hungary
Semmelweis University
🇭🇺
Budapest, Hungary
Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases
🇭🇺
Budapest, Hungary