Community-acquired Pneumonia (CAP)Phase 3NCT03439124
Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia
A Phase 3 study testing ceftobiprole medocaril and IV standard-of-care cephalosporin in people with Community-acquired Pneumonia (CAP) and Hospital-acquired Pneumonia (HAP), run by Basilea Pharmaceutica at 19 sites in 4 countries.
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… Read more about this study
- Who is it for?
- Ages 3 months to 17 years
- Conditions the study is for
- Community-acquired Pneumonia (CAP), Hospital-acquired Pneumonia (HAP)
- What is being tested?
- ceftobiprole medocaril and IV standard-of-care cephalosporin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 19 sitesin 4 countries
- Study dates
- 27 Nov 2017to 16 Mar 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
19 sites in 4 countries.
19 sites in 4 countries
Hungary7 sites
Principal SMO Ltd.
Baja, 6500
Semmelweis University
Budapest, 1094
Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases
Budapest, 1097
Bekes County Central Hospital
Gyula, 5700
Kanizsai Dorottya Hospital
Nagykanizsa, 8800
Fejer County St. Gyorgy University Teaching Hospital
Székesfehérvár, 8000
Torokbalint Pulmonology Institute
Törökbálint, 2045
Georgia6 sites
Amtel Hospital First Clinical LLC
Tbilisi, 0144
LTD High Technology Medical Center University Clinic
Tbilisi, 0144
JSC Evex Hospitals 1
Tbilisi, 0159
JSC Evex Hospitals 2
Tbilisi, 0159
Tbilisi State Medical University G. Zhvania Pediatric Academic Clinic
Tbilisi, 0159
Ltd Tbilisi Pediatric Private Clinic
Tbilisi, 0191
Bulgaria4 sites
University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski"
Pleven, 5800
University Multiprofile Hospital for Active Treatment "Sveti Georgi"
Plovdiv, 4002
Multiprofile Hospital for Active Treatment
Rousse, 7002
University Multiprofile Hospital for Active Treatment "Aleksandrovska"
Sofia, 1431
Romania2 sites
Alessandrescu-Rusescu National Institute for Mother and Child Health
Bucharest, 020395
Sf. Maria" Children's Emergency Clinical Hospital
Iași, 700309
About this study
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
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.
Read the 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.
- Being tested
- ceftobiprole medocaril, IV standard-of-care cephalosporin
- Medical subject headings
- Community-Acquired Pneumonia, Healthcare-Associated Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ceftobiprole medocarilDrug
Also called ceftobiprole
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 cephalosporinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: IV standard-of-care cephalosporin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: At the test-of-cure (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.
Measured: 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.
Measured: 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.
Measured: At Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start27 Nov 2017
- Primary completion16 Mar 2020
- Study completion16 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Community-acquired Pneumonia (CAP)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 138 participants (actual)
Sponsor and investigators
- Lead sponsor
- Basilea Pharmaceutica
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marc Engelhardt, MD, Study director, Basilea Pharmaceutica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439124
- Sponsor's protocol ID
- BPR-PIP-002
- Status last verified
- May 2023
- First submitted
- 30 Jan 2018
- Last updated
- 12 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34533489Bosheva 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.
PubMed 33480665
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03439124
- Acronym / sponsor ID
- BPR-PIP-002
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 138 participants (actual)
- Lead sponsor
- Basilea PharmaceuticaIndustry (pharma, biotech, devices)
- Study start
- 27 Nov 2017 (actual)
- Primary completion
- 16 Mar 2020 (actual)
- Study completion
- 16 Mar 2020 (actual)
- First posted
- 20 Feb 2018 (actual)
- Results
- Posted 11 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ceftobiprole medocaril | Experimental | Drug: ceftobiprole medocarilCeftobiprole 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. |
| IV standard-of-care cephalosporin | Active comparator | Drug: IV standard-of-care cephalosporinCeftriaxone 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. |
Who may qualify
- Ages
- 3 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ceftobiprole medocarilAlso: ceftobiproleCeftobiprole 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. | Drug | Ceftobiprole medocaril |
| IV standard-of-care cephalosporinCeftriaxone 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. | Drug | IV standard-of-care cephalosporin |
Primary outcome
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.
4 secondary outcomes
Proportion of Patients With Clinical Cure in the Intent-to-treat Population (ITT)
Time frame: At the test-of-cure (TOC) visit
Proportion of Patients With Clinical Cure in the Clinically Evaluable (CE) Population
Time frame: At the TOC visit
Proportion of Patients With Early Clinical Response in the Intent-to-treat (ITT) Population
Time frame: At Day 4
Proportion of Patients With Early Clinical Response in the Clinically Evaluable (CE) Population
Time frame: At Day 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34533489Rubino 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.
- Derived from this study: PubMed 33480665Bosheva 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Engelhardt, MD study director
Basilea Pharmaceutica
19 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ceftobiprole medocaril and IV standard-of-care cephalosporin in people with Community-acquired Pneumonia (CAP) and Hospital-acquired Pneumonia (HAP), run by Basilea Pharmaceutica at 19 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Hungary, Georgia, Bulgaria, Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03439124, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2023.