Late-onset SepsisPhase 2NCT02424734
Safety, Tolerability and Efficacy of Ceftaroline in Paediatrics With Late-Onset Sepsis
A Phase 2 study testing Ceftaroline Fosamil, Ampicillin and Aminoglycoside in people with Late-onset Sepsis, run by Pfizer at 4 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of ceftaroline for the treatment of Late Onset Sepsis in neonates and young infants aged 7 to <60 days Read more about this study
- Who is it for?
- Ages 7 to 59 days
- Conditions the study is for
- Late-onset Sepsis
- What is being tested?
- Ceftaroline Fosamil, Ampicillin and Aminoglycoside
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 4 Aug 2015to 26 Dec 2017
- Phase
- Phase 2
- 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 7 to 59 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Informed consent in writing from parent(s) or other legally-acceptable representative(s);
- Male or female, gestational age ≥34 weeks, and chronological age 7 to <60 days at the time of screening;
- Diagnosis of sepsis within 36 hours before enrolment, defined as the presence of at least 2 clinical criteria and at least 1 laboratory criterion in the presence of or as a result of suspected or proven bacterial infection that requires IV antibiotic therapy;
- Patients must meet at least 2 of the following clinical criteria :Hypothermia (<36°C) OR fever (>38.5°C); Bradycardia OR tachycardia OR rhythm instability; Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral perfusion; Petechial rash OR sclerema neonatorum; New onset or worsening of apnoea episodes OR tachypnoea episodes OR increased oxygen requirements OR requirement for ventilation support; Feeding intolerance OR poor sucking OR abdominal distension; Irritability; Lethargy; Hypotonia:
- Patients must meet at least 1 of the following laboratory criteria: White blood cell count ≤4,000 × 109/L OR ≥20,000 × 109/L; Immature to total neutrophil ratio >0.2; Platelet count ≤100,000 × 109/L; C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥2 ng/mL; Hyperglycaemia OR Hypoglycaemia; Metabolic acidosis.
Who cannot join
- Documented history of any hypersensitivity or allergic reaction to any β-lactam antibiotic or aminoglycoside;
- At study entry, has confirmed infection with a pathogen known to be resistant to the combination of ceftaroline fosamil, ampicillin, and the optional aminoglycoside of choice OR confirmed viral, fungal, or parasitic pathogen as the sole cause of infection;
- Refractory septic shock within 24 hours before enrolment that does not resolve after 60 minutes of vasopressor therapy;
- Moderate or severe renal impairment defined as serum creatinine ≥2 times the upper limit of normal (× ULN) for age OR urine output <0.5 mL/kg/h (measured over at least 8 hours) OR requirement for dialysis;
- Evidence of progressively fatal underlying disease, or life expectancy of ≤60 days;
- Documented history of seizure;
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- Requiring or currently taking antiretroviral therapy for human immunodeficiency virus (HIV) or a child from an HIV positive mother;
- Proven or suspected central nervous system (CNS) infection (eg, meningitis, brain abscess, subdural abscess), osteomyelitis, endocarditis, or necrotizing enterocolitis (NEC);
- Any condition (eg, cystic fibrosis, urea cycle disorders), antepartum/peripartum factors, or procedures that would, in the opinion of the investigator, make the patient unsuitable for the study, place a patient at risk, or compromise the quality of data;
- Patient's parent(s) or legally-acceptable representative(s) involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Concurrent participation in another clinical study with an investigational product (IP), previous enrolment/participation in this study, or participation in another study of ceftaroline fosamil within 14 days before the intended start of the first dose of study therapy.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Hungary3 sites
Egyesitett Szent Istvan es Szent Laszlo Korhaz - Rendelointezet, Gyermekinfektologiai Osztaly
Budapest, 1097
Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak, Gyermek-, Koraszulott es Csecsemoosztaly
Budapest, 1125
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Gyermekosztaly
Nyíregyháza, 4400
United States1 site
Rady Children's Hospital San Diego
San Diego, California, 92123
About this study
Official title: Open-label, Multicentre Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Efficacy Of Ceftaroline In Neonates And Young Infants With Late-onset Sepsis
The purpose of this study is to evaluate the safety and tolerability of ceftaroline for the treatment of Late Onset Sepsis in neonates and young infants aged 7 to <60 days
Read the detailed description
This is a multicentre, multinational, open-label, single treatment arm study of intravenous (IV) ceftaroline fosamil and ampicillin, plus an optional aminoglycoside of choice, in hospitalized neonates and young infants aged 7 to < 60 days with late-onset sepsis (LOS).
Baseline assessments for study eligibility will occur within 36 hours before administration of the first dose of study therapy. Study Day 1 is defined as the 24-hour period starting at the onset of the first administration of study therapy. Thereafter, subsequent Study Days are to follow the same pattern.
Safety assessments will occur throughout the study. Clinical outcome evaluations will occur at End-of-Therapy (EOT; within 24 hours after completion of last infusion) and Test-of-Cure (TOC; 8 to 15 days after the last dose of study therapy).
- Conditions
- Late-onset Sepsis
- Being tested
- Ceftaroline Fosamil, Ampicillin, Aminoglycoside
- Keywords
- Late-onset Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftaroline FosamilDrug
Also called Zinforo, Teflaro
Ceftaroline fosamil will be given at a dose of 6 mg/kg IV over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour).
AmpicillinDrug
Ampicillin IV is required for the first 48 hours if the presence of an organism that requires treatment with ampicillin cannot be excluded. Will be given as per local standard of care.
AminoglycosideDrug
Optional, will be given as per local standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Ceftaroline Fosamil | Experimental | Ceftaroline Fosamil Receives: Drug: Ceftaroline Fosamil; Drug: Ampicillin; Drug: Aminoglycoside |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to study follow-up (SFU) visit (28 to 35 days after last dose of study treatment) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Measured: Baseline up to SFU visit (up to a maximum study duration of 49 days)
Secondary outcomes (5)
Plasma Concentration of Ceftaroline Fosamil
Data was not summarized and provided for individual participants only and reported in this end point for only those participants who had concentrations above limit of quantification (LOQ). LOQ was 50 nanogram per milliliter (ng/mL).
Measured: At the end of infusion (EOI)
Plasma Concentration of Ceftaroline
Ceftaroline fosamil was the prodrug of ceftaroline. Data was not summarized and provided for individual participants only and reported in this end point for only those participants who had concentrations above LOQ at any specific time-point. LOQ was 50 ng/mL
Measured: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI
Plasma Concentration of Ceftaroline M-1
Ceftaroline M-1 was the inactive metabolite of ceftaroline. Data was not summarized and provided for individual participants only and reported in this end point for only those participants who had concentrations above LOQ at any specific time-point. LOQ was 50 ng/mL
Measured: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI
Percentage of Participants With Favorable Clinical Response
Clinical response was assessed by the investigator as Cure, Failure or Indeterminate at End of treatment (EOT) and Test of Cure (TOC). Favorable clinical response was defined as clinical response of Cure (defined as resolution of all acute signs and symptoms of Late-onset sepsis [LOS] or improvement to such an extent that no further antibacterial therapy is required). EOT visit occurred within 24 hours after the end of last infusion. TOC visit occurred within 8 to 15 days after the last dose of study therapy.
Measured: EOT visit (up to Day 15), TOC visit (up to Day 29)
Percentage of Participants With Favorable Microbiological Response
Microbiological response was determining programmatically and assessed at the participants level at EOT and TOC. Microbiological response was defined as Favorable (Eradication or Presumed Eradication), Unfavorable (Persistence or Presumed Persistence) or Indeterminate (participant's clinical response is Indeterminate and no microbiological culture data is available). Eradication defined as absence of the original baseline pathogen from the source specimen; presumed eradication was defined when source specimen was not available to culture and the participant was assessed as a clinical cure (resolution of all acute signs and symptoms of LOS or improvement to such an extent that no further antibacterial therapy was required). EOT visit occurred within 24 hours after the end of last infusion. TOC visit occurred within 8 to 15 days after last dose of study drug.
Measured: EOT visit (up to Day 15), TOC visit (up to Day 29)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2015 (estimated)
- Study start4 Aug 2015
- Primary completion26 Dec 2017
- Study completion26 Dec 2017
Why it stopped: Study was terminated on 22Dec2017 due to slow enrollment; there were no safety or efficacy concerns.
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 (1)Papers the sponsor has linked to this study.
- Other trials for Late-onset SepsisStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02424734
- Sponsor's protocol ID
- D3720C00009
- Other IDs
- C2661002, 2014-003243-34, 2014
- Status last verified
- Aug 2018
- First submitted
- 23 Feb 2015
- Last updated
- 13 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bradley JS, Stone GG, Chan PLS, Raber SR, Riccobene T, Mas Casullo V, Yan JL, Hendrick VM, Hammond J, Leister-Tebbe HK. Phase 2 Study of the Safety, Pharmacokinetics and Efficacy of Ceftaroline Fosamil in Neonates and Very Young Infants With Late-onset Sepsis. Pediatr Infect Dis J. 2020 May;39(5):411-418. doi: 10.1097/INF.0000000000002607.
PubMed 32091493
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Multicentre Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Efficacy Of Ceftaroline In Neonates And Young Infants With Late-onset Sepsis
- ClinicalTrials.gov ID
- NCT02424734
- Acronym / sponsor ID
- D3720C00009
- Conditions
- Late-onset Sepsis
- Keywords
- Late-onset Sepsis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated on 22Dec2017 due to slow enrollment; there were no safety or efficacy concerns.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 4 Aug 2015 (actual)
- Primary completion
- 26 Dec 2017 (actual)
- Study completion
- 26 Dec 2017 (actual)
- First posted
- 23 Apr 2015 (estimated)
- Results
- Posted 17 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of ceftaroline for the treatment of Late Onset Sepsis in neonates and young infants aged 7 to <60 days
Detailed description
This is a multicentre, multinational, open-label, single treatment arm study of intravenous (IV) ceftaroline fosamil and ampicillin, plus an optional aminoglycoside of choice, in hospitalized neonates and young infants aged 7 to < 60 days with late-onset sepsis (LOS).
Baseline assessments for study eligibility will occur within 36 hours before administration of the first dose of study therapy. Study Day 1 is defined as the 24-hour period starting at the onset of the first administration of study therapy. Thereafter, subsequent Study Days are to follow the same pattern.
Safety assessments will occur throughout the study. Clinical outcome evaluations will occur at End-of-Therapy (EOT; within 24 hours after completion of last infusion) and Test-of-Cure (TOC; 8 to 15 days after the last dose of study therapy).
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ceftaroline Fosamil | Experimental | Drug: Ceftaroline Fosamil, Drug: Ampicillin, Drug: AminoglycosideCeftaroline Fosamil |
Who may qualify
- Ages
- 7 to 59 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Informed consent in writing from parent(s) or other legally-acceptable representative(s);
- Male or female, gestational age ≥34 weeks, and chronological age 7 to <60 days at the time of screening;
- Diagnosis of sepsis within 36 hours before enrolment, defined as the presence of at least 2 clinical criteria and at least 1 laboratory criterion in the presence of or as a result of suspected or proven bacterial infection that requires IV antibiotic therapy;
- Patients must meet at least 2 of the following clinical criteria :Hypothermia (<36°C) OR fever (>38.5°C); Bradycardia OR tachycardia OR rhythm instability; Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral perfusion; Petechial rash OR sclerema neonatorum; New onset or worsening of apnoea episodes OR tachypnoea episodes OR increased oxygen requirements OR requirement for ventilation support; Feeding intolerance OR poor sucking OR abdominal distension; Irritability; Lethargy; Hypotonia:
- Patients must meet at least 1 of the following laboratory criteria: White blood cell count ≤4,000 × 109/L OR ≥20,000 × 109/L; Immature to total neutrophil ratio >0.2; Platelet count ≤100,000 × 109/L; C-reactive protein (CRP) >15 mg/L OR procalcitonin ≥2 ng/mL; Hyperglycaemia OR Hypoglycaemia; Metabolic acidosis.
Key exclusion criteria (10 listed)
- Documented history of any hypersensitivity or allergic reaction to any β-lactam antibiotic or aminoglycoside;
- At study entry, has confirmed infection with a pathogen known to be resistant to the combination of ceftaroline fosamil, ampicillin, and the optional aminoglycoside of choice OR confirmed viral, fungal, or parasitic pathogen as the sole cause of infection;
- Refractory septic shock within 24 hours before enrolment that does not resolve after 60 minutes of vasopressor therapy;
- Moderate or severe renal impairment defined as serum creatinine ≥2 times the upper limit of normal (× ULN) for age OR urine output <0.5 mL/kg/h (measured over at least 8 hours) OR requirement for dialysis;
- Evidence of progressively fatal underlying disease, or life expectancy of ≤60 days;
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 |
|---|---|---|
| Ceftaroline FosamilAlso: Zinforo, TeflaroCeftaroline fosamil will be given at a dose of 6 mg/kg IV over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour). | Drug | Ceftaroline Fosamil |
| AmpicillinAmpicillin IV is required for the first 48 hours if the presence of an organism that requires treatment with ampicillin cannot be excluded. Will be given as per local standard of care. | Drug | Ceftaroline Fosamil |
| AminoglycosideOptional, will be given as per local standard of care. | Drug | Ceftaroline Fosamil |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
Time frame: Baseline up to SFU visit (up to a maximum study duration of 49 days)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to study follow-up (SFU) visit (28 to 35 days after last dose of study treatment) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
5 secondary outcomes
Plasma Concentration of Ceftaroline Fosamil
Time frame: At the end of infusion (EOI)
Plasma Concentration of Ceftaroline
Time frame: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI
Plasma Concentration of Ceftaroline M-1
Time frame: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI
Percentage of Participants With Favorable Clinical Response
Time frame: EOT visit (up to Day 15), TOC visit (up to Day 29)
Percentage of Participants With Favorable Microbiological Response
Time frame: EOT visit (up to Day 15), TOC visit (up to Day 29)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32091493Bradley JS, Stone GG, Chan PLS, Raber SR, Riccobene T, Mas Casullo V, Yan JL, Hendrick VM, Hammond J, Leister-Tebbe HK. Phase 2 Study of the Safety, Pharmacokinetics and Efficacy of Ceftaroline Fosamil in Neonates and Very Young Infants With Late-onset Sepsis. Pediatr Infect Dis J. 2020 May;39(5):411-418. doi: 10.1097/INF.0000000000002607.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Pfizer CT.gov Call Center study director
Pfizer
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ceftaroline Fosamil, Ampicillin and Aminoglycoside in people with Late-onset Sepsis, run by Pfizer at 4 sites in 2 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 10 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: stopped early, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Hungary, United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 17 Jul 2018). 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?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs) (time frame: Baseline up to SFU visit (up to a maximum study duration of 49 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 NCT02424734, which also lists 1 linked publication.
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 13 Sep 2018.