Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

Community-acquired Pneumonia (CAP) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03439124
• Other study ID #: BPR-PIP-002
• Status: Completed
• Phase: Phase 3
• Start date: November 27, 2017
• Est. completion date: March 16, 2020

Study information

• Verified date: May 2023
• Source: Basilea Pharmaceutica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: March 16, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 17 Years

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 <0.5x10?/L; platelet count <50x10?/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

Related Conditions & MeSH terms

• Community-acquired Pneumonia (CAP)
• Healthcare-Associated Pneumonia
• Hospital-acquired Pneumonia (HAP)
• Pneumonia

Intervention

Drug:
• ceftobiprole medocaril
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.
• IV standard-of-care cephalosporin
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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Basilea Pharmaceutica

Countries where clinical trial is conducted

Bulgaria,  Georgia,  Hungary,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Analysis of AEs assessed during the first 3 days of IV therapy and while on IV, a median of 7 days
Secondary	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.	At the test-of-cure (TOC) visit
Secondary	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.	At the TOC visit
Secondary	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.	At Day 4
Secondary	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.	At Day 4