Clinical trial NCT02424734: Safety, Tolerability and Efficacy of Ceftaroline in Paediatrics With Late-Onset Sepsis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Late-onset Sepsis
Keywords: Late-onset Sepsis
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2015-04-23
Enrollment: 11
Sex: ALL
Minimum age (years): 7
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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

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).

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Discontinuations Due to Adverse Events (AEs)
timeFrame: Baseline up to SFU visit (up to a maximum study duration of 49 days)
Secondary outcomes:
measure: Plasma Concentration of Ceftaroline Fosamil
timeFrame: At the end of infusion (EOI)
measure: Plasma Concentration of Ceftaroline
timeFrame: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI
measure: Plasma Concentration of Ceftaroline M-1
timeFrame: At EOI, 15 minutes to 2 hours, 3 to 4 hours and 5 to 7 hours after EOI
measure: Percentage of Participants With Favorable Clinical Response
timeFrame: EOT visit (up to Day 15), TOC visit (up to Day 29)
measure: Percentage of Participants With Favorable Microbiological Response
timeFrame: EOT visit (up to Day 15), TOC visit (up to Day 29)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital San Diego
state: California
city: Budapest
country: Hungary
facility: Egyesitett Szent Istvan es Szent Laszlo Korhaz - Rendelointezet, Gyermekinfektologiai Osztaly
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak, Gyermek-, Koraszulott es Csecsemoosztaly
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Gyermekosztaly
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.