Safety, Tolerability and Efficacy of Ceftaroline in Paediatrics With Late-Onset Sepsis

NCT02424734 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: D3720C00009C26610022014-003243-34
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 4

Brief 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

Conditions

Late-onset Sepsis

Keywords

Late-onset Sepsis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline up to SFU visit (up to a maximum study duration of 49 days)

Secondary Outcomes (5)

• Plasma Concentration of Ceftaroline Fosamil

  At the end of infusion (EOI)

• Plasma Concentration of Ceftaroline

  At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI

• Plasma Concentration of Ceftaroline M-1

  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

  EOT visit (up to Day 15), TOC visit (up to Day 29)

• Percentage of Participants With Favorable Microbiological Response

  EOT visit (up to Day 15), TOC visit (up to Day 29)

Study Arms (1)

Ceftaroline Fosamil

EXPERIMENTAL

Ceftaroline Fosamil

Drug: Ceftaroline Fosamil; Drug: Ampicillin; Drug: Aminoglycoside

Interventions

Ceftaroline Fosamil DRUG

Ceftaroline fosamil will be given at a dose of 6 mg/kg IV over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour).

Also known as: Zinforo, Teflaro

Ceftaroline Fosamil

Ampicillin DRUG

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.

Ceftaroline Fosamil

Aminoglycoside DRUG

Optional, will be given as per local standard of care.

Ceftaroline Fosamil

Eligibility Criteria

• Age: 7 Days - 59 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Pfizer: lead
• PRA Health Sciences: collaborator

Study Sites (4)

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Egyesitett Szent Istvan es Szent Laszlo Korhaz - Rendelointezet, Gyermekinfektologiai Osztaly

Budapest, 1097, Hungary

Location

Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak, Gyermek-, Koraszulott es Csecsemoosztaly

Budapest, 1125, Hungary

Location

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Gyermekosztaly

Nyíregyháza, 4400, Hungary

Location

Related Publications (1)

• 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.

  PMID: 32091493 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Ceftaroline; Ampicillin; Aminoglycosides

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Penicillin G; Penicillins; Glycosides; Carbohydrates

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: April 23, 2015
• Study Start: August 4, 2015
• Primary Completion: December 26, 2017
• Study Completion: December 26, 2017
• Last Updated: September 13, 2018
• Results First Posted: July 17, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); HU (3)