Neonatal Vancomycin Trial (NeoVanc)
Late Onset Neonatal Sepsis
About this trial
This is an interventional treatment trial for Late Onset Neonatal Sepsis focused on measuring sepsis, neonate, vancomycin
Eligibility Criteria
Inclusion Criteria:
- Postnatal age ≤ 90 days AND
- Postnatal age ≥ 72 hours at onset of sepsis AND
- Clinical sepsis as defined by presence of any three clinical or laboratory criteria from the list below OR
- Confirmed, significant bacterial sepsis as defined by positive culture with a Gram-positive bacterium from a normally sterile site and at least one clinical or one laboratory criterion from the list below, in the 24 hours before randomisation
Clinical criteria
- hyper- or hypothermia,
- hypotension or impaired peripheral perfusion or mottled skin,
- apnoea or increased oxygen requirement or increased requirement for ventilatory support,
- bradycardic episodes or tachycardia,
- worsening feeding intolerance or abdominal distension,
- lethargy or hypotonia or irritability
Laboratory criteria:
- white blood cell (WBC) count < 4 or > 20 x 109 cells/L
- immature to total neutrophil ratio (I/T) > 0.2
- platelet count < 100 x 109/L
- C-reactive protein (CRP) > 10 mg/L
- glucose intolerance as defined by a blood glucose value > 180 mg/dL (> 10 mmol/L) when receiving normal glucose amounts (8 - 15 g/kg/day)
- metabolic acidosis as defined by a base excess (BE) < -10 mmol/L (-10 mEq/L) or a blood lactate value > 2 mmol/L
Exclusion Criteria:
- Administration of any systemic antibiotic regimen for more than 24 hours prior to randomisation, unless the change is driven by the apparent lack of efficacy of the original regimen
- Treatment with vancomycin for ≥ 24 hours at any time within 7 days of enrolment
- Known toxicity, hypersensitivity or intolerance to vancomycin
- Known renal impairment with urinary output < 0.7 ml/kg/hour for 24 hours or a creatinine value ≥ 100 µmol/L (1.13 mg/dL)
- Patient receiving (or planned to receive) haemofiltration, haemodialysis, peritoneal dialysis, extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass
- Severe congenital malformations where the infant is not expected to survive for more than 3 months
- Patient known to have S. aureus (MSSA or MRSA) bacteraemia
- Patient with osteomyelitis, septic arthritis, urinary tract infection (UTI) or meningitis
- Patient with high suspicion of/confirmed sepsis caused by Gram-negative organisms or fungi
- Other situations where the treating physician considers a different empiric antibiotic regimen necessary
- Current participation in any other clinical study of an investigational medicinal product (IMP)
Post-randomisation exclusions
• Any participant found to have Gram-negative or fungal sepsis, osteomyelitis, septic arthritis, UTI, meningitis or S. aureus (MSSA or MRSA) bacteraemia after randomisation will be excluded from analysis. Participants who have received at least one dose of study vancomycin will be followed up for safety
Sites / Locations
- Tallinn's Children's Hospital
- Paediatric Intensive Care Unit, Clinicum of the University of Tartu
- Aghia Sophia Children's Hospital (A)
- Aghia Sophia Children's Hospital (B)
- Aghia Sophia Children's Hospital (C)
- Kyriakou Children's Hospital
- General University Hospital Attikon
- Hippokration Hospital - Department of Neonatology
- Papageorgiou 2nd Department of Neonatology
- Ospedale "Di Venere" - Carbonara di Bari
- ASST Grande Ospedale Metropolitano Niguarda
- Azienda Ospedaliera di Padova
- Policlinico San Matteo
- Ospedale Pediatrico Bambino Gesu'
- Hospital Sant Joan de Deu
- Hospital 12 de Octubre
- Hospital Materno Infantil, La Paz
- St Mary's Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Vancomycin - Optimised Regimen
Vancomycin - Standard Regimen
A single loading dose of 25 mg/kg followed by a maintenance dose of: Postmenstrual age ≤ 35 weeks - 15 mg/kg 12 hourly; Postmenstrual age > 35 weeks - 15 mg/kg 8 hourly
Postmenstrual age < 29 weeks - 15 mg/kg given 24 hourly; Postmenstrual age 29 - 35 weeks - 15 mg/kg 12 hourly; Postmenstrual age > 35 weeks - 15 mg/kg 8 hourly