Back to resultsCeftobiprole in the Treatment of Pediatric Patients With Pneumonia
Primary Purpose
Community-acquired Pneumonia (CAP), Hospital-acquired Pneumonia (HAP)
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ceftobiprole medocaril
IV standard-of-care cephalosporin
Sponsored by
About this trial
This is an interventional treatment trial for Community-acquired Pneumonia (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
Sites / Locations
- University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
- University Multiprofile Hospital for Active Treatment "Sveti Georgi"
- Multiprofile Hospital for Active Treatment
- University Multiprofile Hospital for Active Treatment "Aleksandrovska"
- Amtel Hospital First Clinical LLC
- LTD High Technology Medical Center University Clinic
- JSC Evex Hospitals 1
- JSC Evex Hospitals 2
- Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic
- Ltd Tbilisi Pediatric Private Clinic
- Principal SMO Ltd.
- Semmelweis University
- Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases
- Bekes County Central Hospital
- Kanizsai Dorottya Hospital
- Fejer County St. Gyorgy University Teaching Hospital
- Torokbalint Pulmonology Institute
- Alessandrescu-Rusescu National Institute for Mother and Child Health
- Sf. Maria" Children's Emergency Clinical Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ceftobiprole medocaril
IV standard-of-care cephalosporin
Arm 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.
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.
Outcomes
Primary Outcome Measures
Adverse Events
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
Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)
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 Clinical Cure in the Clinically Evaluable (CE) Population
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.
Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population
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
Comparison of early clinical response rates in the CE population between ceftobiprole and the comparator at Day 4.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03439124
Brief Title
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 27, 2017 (Actual)
Primary Completion Date
March 16, 2020 (Actual)
Study Completion Date
March 16, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Basilea Pharmaceutica
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Community-acquired Pneumonia (CAP), Hospital-acquired Pneumonia (HAP)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
138 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ceftobiprole medocaril
Arm Type
Experimental
Arm 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.
Arm Title
IV standard-of-care cephalosporin
Arm Type
Active Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
ceftobiprole medocaril
Other Intervention Name(s)
ceftobiprole
Intervention Description
Ceftobiprole medocaril was administered at age-adjusted doses (10, 15 or 20 mg/kg) and infusion durations (2 or 4 hours) every 8 hours. The maximum dose, regardless of body weight, was 500 mg ceftobiprole every 8 hours (maximum total daily dose of 1500 mg ceftobiprole).
After a minimum of 3 days of IV treatment, patients with sufficient improvement in disease signs and symptoms could be switched to an age-appropriate oral antibiotic to complete a total minimum of 7 days and a total maximum of 14 days' antibiotic treatment.
Intervention Type
Drug
Intervention Name(s)
IV standard-of-care cephalosporin
Intervention Description
Ceftriaxone was administered at 50 to 80 mg/kg IV as a single daily dose, up to a maximum dose of 2 g/day. The actual dose of ceftriaxone within this dose range was determined by the blinded investigator prior to first study drug administration and was not modified during subsequent study days.
After a minimum of 3 days of IV treatment, patients with sufficient improvement in disease signs and symptoms could be switched to an age-appropriate oral antibiotic to complete a total minimum of 7 days and a total maximum of 14 days' antibiotic treatment.
At the discretion of the blinded investigator, patients received vancomycin at a dose of 10 to 15 mg/kg IV every 6 hours, up to a maximum dose of 2 g/day, in addition to the IV standard-of-care cephalosporin when MRSA was suspected or confirmed.
Primary Outcome Measure Information:
Title
Adverse Events
Description
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.
Time Frame
Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days
Secondary Outcome Measure Information:
Title
Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)
Description
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.
Time Frame
At the test-of-cure (TOC) visit
Title
Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population
Description
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.
Time Frame
At the TOC visit
Title
Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population
Description
Comparison of early clinical response rates in the ITT population between ceftobiprole and the comparator at Day 4.
Time Frame
At Day 4
Title
Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population
Description
Comparison of early clinical response rates in the CE population between ceftobiprole and the comparator at Day 4.
Time Frame
At Day 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Engelhardt, MD
Organizational Affiliation
Basilea Pharmaceutica
Official's Role
Study Director
Facility Information:
Facility Name
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment "Sveti Georgi"
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment "Aleksandrovska"
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Amtel Hospital First Clinical LLC
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
LTD High Technology Medical Center University Clinic
City
Tbilisi
ZIP/Postal Code
0144
Country
Georgia
Facility Name
JSC Evex Hospitals 1
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
JSC Evex Hospitals 2
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic
City
Tbilisi
ZIP/Postal Code
0159
Country
Georgia
Facility Name
Ltd Tbilisi Pediatric Private Clinic
City
Tbilisi
ZIP/Postal Code
0191
Country
Georgia
Facility Name
Principal SMO Ltd.
City
Baja
ZIP/Postal Code
6500
Country
Hungary
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1094
Country
Hungary
Facility Name
Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
Bekes County Central Hospital
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
Facility Name
Kanizsai Dorottya Hospital
City
Nagykanizsa
ZIP/Postal Code
8800
Country
Hungary
Facility Name
Fejer County St. Gyorgy University Teaching Hospital
City
Szekesfehervar
ZIP/Postal Code
8000
Country
Hungary
Facility Name
Torokbalint Pulmonology Institute
City
Torokbalint
ZIP/Postal Code
2045
Country
Hungary
Facility Name
Alessandrescu-Rusescu National Institute for Mother and Child Health
City
Bucharest
ZIP/Postal Code
020395
Country
Romania
Facility Name
Sf. Maria" Children's Emergency Clinical Hospital
City
Iaşi
ZIP/Postal Code
700309
Country
Romania
12. IPD Sharing Statement
Citations:
PubMed Identifier
34533489
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.
Results Reference
derived
PubMed Identifier
33480665
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.
Results Reference
derived
Learn more about this trial
Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia
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