Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

NCT03439124 | Completed Phase 3 Results DMC

• 1 other identifier: BPR-PIP-002
• Study Type: interventional
• Target: 138
• Locations: 4 countries
• Sites: 19

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)

  At the test-of-cure (TOC) visit

• Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population

  At the TOC visit

• Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population

  At Day 4

• Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population

  At Day 4

Study Arms (2)

Ceftobiprole medocaril

EXPERIMENTAL

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.

Drug: ceftobiprole medocaril

IV standard-of-care cephalosporin

ACTIVE COMPARATOR

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.

Drug: IV standard-of-care cephalosporin

Interventions

ceftobiprole medocaril DRUG

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.

Also known as: ceftobiprole

Ceftobiprole medocaril

IV standard-of-care cephalosporin DRUG

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.

IV standard-of-care cephalosporin

Eligibility Criteria

• Age: 3 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (19)

University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"

Pleven, 5800, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Sveti Georgi"

Plovdiv, 4002, Bulgaria

Location

Multiprofile Hospital for Active Treatment

Rousse, 7002, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Aleksandrovska"

Sofia, 1431, Bulgaria

Location

Amtel Hospital First Clinical LLC

Tbilisi, 0144, Georgia

Location

LTD High Technology Medical Center University Clinic

Tbilisi, 0144, Georgia

Location

JSC Evex Hospitals 1

Tbilisi, 0159, Georgia

Location

JSC Evex Hospitals 2

Tbilisi, 0159, Georgia

Location

Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic

Tbilisi, 0159, Georgia

Location

Ltd Tbilisi Pediatric Private Clinic

Tbilisi, 0191, Georgia

Location

Principal SMO Ltd.

Baja, 6500, Hungary

Location

Semmelweis University

Budapest, 1094, Hungary

Location

Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases

Budapest, 1097, Hungary

Location

Bekes County Central Hospital

Gyula, 5700, Hungary

Location

Kanizsai Dorottya Hospital

Nagykanizsa, 8800, Hungary

Location

Fejer County St. Gyorgy University Teaching Hospital

Székesfehérvár, 8000, Hungary

Location

Torokbalint Pulmonology Institute

Törökbálint, 2045, Hungary

Location

Alessandrescu-Rusescu National Institute for Mother and Child Health

Bucharest, 020395, Romania

Location

Sf. Maria" Children's Emergency Clinical Hospital

Iași, 700309, Romania

Location

Related Publications (2)

• 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.

  PMID: 34533489 DERIVED

• 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.

  PMID: 33480665 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia; Healthcare-Associated Pneumonia

Interventions

ceftobiprole medocaril; ceftobiprole

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Cross Infection; Lung Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Project Physician
• Organization: Basilea Pharmaceutica International Ltd.

marc.engelhardt@basilea.com

+41 79 701 0551

Study Officials

• Marc Engelhardt, MD

  Basilea Pharmaceutica

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 20, 2018
• Study Start: November 27, 2017
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: May 12, 2023
• Results First Posted: September 11, 2020

Record last verified: 2023-05

Locations

HU (7); RO (2); GE (6); BU (4)