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Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03439124
Recruitment Status : Completed
First Posted : February 20, 2018
Results First Posted : September 11, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Basilea Pharmaceutica

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.

Condition or disease Intervention/treatment Phase
Community-acquired Pneumonia (CAP) Hospital-acquired Pneumonia (HAP) Drug: ceftobiprole medocaril Drug: IV standard-of-care cephalosporin Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 27, 2017
Actual Primary Completion Date : March 16, 2020
Actual Study Completion Date : March 16, 2020


Arm Intervention/treatment
Experimental: 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.
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.

Other Name: ceftobiprole

Active Comparator: 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.

Drug: 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.





Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 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 :
  1. Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT) [ Time Frame: 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.

  2. Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population [ Time Frame: 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.

  3. Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population [ Time Frame: At Day 4 ]
    Comparison of early clinical response rates in the ITT population between ceftobiprole and the comparator at Day 4.

  4. Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population [ Time Frame: At Day 4 ]
    Comparison of early clinical response rates in the CE population between ceftobiprole and the comparator at Day 4.



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Ages Eligible for Study:   3 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03439124


Locations
Show Show 19 study locations
Sponsors and Collaborators
Basilea Pharmaceutica
Investigators
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Study Director: Kamal Hamed, MD, MPH Basilea Pharmaceutica
  Study Documents (Full-Text)

Documents provided by Basilea Pharmaceutica:
Study Protocol  [PDF] November 29, 2018
Statistical Analysis Plan  [PDF] March 2, 2020

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Responsible Party: Basilea Pharmaceutica
ClinicalTrials.gov Identifier: NCT03439124    
Other Study ID Numbers: BPR-PIP-002
First Posted: February 20, 2018    Key Record Dates
Results First Posted: September 11, 2020
Last Update Posted: October 8, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Healthcare-Associated Pneumonia
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Iatrogenic Disease
Disease Attributes
Pathologic Processes
Ceftobiprole
Ceftobiprole medocaril
Cephalosporins
Anti-Bacterial Agents
Anti-Infective Agents