Safety, Tolerability and Efficacy of Ceftaroline in Paediatrics With Late-Onset Sepsis
Condition: Late-onset Sepsis
MeSH terms: Sepsis; Toxemia
Intervention: Ceftaroline Fosamil; Ampicillin; Aminoglycoside
Intervention description: Ceftaroline fosamil will be given at a dose of 6 mg/kg IV over 60 (± 10) minutes every 8 hours (q8h) (± 1 hour).; 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.; Optional, will be given as per local standard of care.
Intervention MeSH terms: Ampicillin; Ceftaroline fosamil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 7 Days
Maximum age: 59 Days
Healthy volunteers: No
Keywords: Late-onset Sepsis

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
    

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.