Clinical trial NCT03439124: Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia
Official title: A Multicentre, Randomized, Investigator-blind, Active-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Ceftobiprole Versus Intravenous Standard-of-care Cephalosporin Treatment With or Without Vancomycin in Pediatric Patients Aged From 3 Months to Less Than 18 Years With Hospital-acquired Pneumonia or Community-acquired Pneumonia Requiring Hospitalisation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Community-acquired Pneumonia (CAP)
Hospital-acquired Pneumonia (HAP)
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
First posted: 2018-02-20
Enrollment: 138
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days
Secondary outcomes:
measure: Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)
timeFrame: At the test-of-cure (TOC) visit
measure: Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population
timeFrame: At the TOC visit
measure: Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population
timeFrame: At Day 4
measure: Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population
timeFrame: At Day 4
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi"
city: Ruse
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Aleksandrovska"
city: Tbilisi
country: Georgia
facility: Amtel Hospital First Clinical LLC
city: Tbilisi
country: Georgia
facility: LTD High Technology Medical Center University Clinic
city: Tbilisi
country: Georgia
facility: JSC Evex Hospitals 1
city: Tbilisi
country: Georgia
facility: JSC Evex Hospitals 2
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi Pediatric Private Clinic
city: Baja
country: Hungary
facility: Principal SMO Ltd.
city: Budapest
country: Hungary
facility: Semmelweis University
city: Budapest
country: Hungary
facility: Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases
city: Gyula
country: Hungary
facility: Bekes County Central Hospital
city: Nagykanizsa
country: Hungary
facility: Kanizsai Dorottya Hospital
city: Szekesfehervar
country: Hungary
facility: Fejer County St. Gyorgy University Teaching Hospital
city: Torokbalint
country: Hungary
facility: Torokbalint Pulmonology Institute
city: Bucharest
country: Romania
facility: Alessandrescu-Rusescu National Institute for Mother and Child Health
city: Iaşi
country: Romania
facility: Sf. Maria" Children's Emergency Clinical Hospital
Study officials:
affiliation: Basilea Pharmaceutica
name: Marc Engelhardt, MD
role: STUDY_DIRECTOR
References:
citation: Rubino CM, Polak M, Schropf S, Munch HG, Smits A, Cossey V, Tomasik T, Kwinta P, Snariene R, Liubsys A, Gardovska D, Hornik CD, Bosheva M, Ruehle C, Litherland K, Hamed K. Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients. Pediatr Infect Dis J. 2021 Nov 1;40(11):997-1003. doi: 10.1097/INF.0000000000003296.
citation: Bosheva M, Gujabidze R, Karoly E, Nemeth A, Saulay M, Smart JI, Hamed KA. A Phase 3, Randomized, Investigator-blinded Trial Comparing Ceftobiprole With a Standard-of-care Cephalosporin, With or Without Vancomycin, for the Treatment of Pneumonia in Pediatric Patients. Pediatr Infect Dis J. 2021 Jun 1;40(6):e222-e229. doi: 10.1097/INF.0000000000003077.