Neonatal Vancomycin Trial

• Status: Terminated
• Trial end date: 2020-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The study aims to compare the efficacy, safety and pharmacokinetics (PK) of an optimised dosing to a standard dosing regimen of vancomycin in neonates and infants aged ≤ 90 days with late onset bacterial sepsis known or suspected to be caused by Gram-positive microorganisms

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PENTA Foundation
• Collaborators: Aristotle University Of Thessaloniki; Bambino Gesù Hospital and Research Institute; Cardiff University; Consorzio per Valutazioni Biologiche e Farmacologiche; European Commission; Institut National de la Santé Et de la Recherche Médicale, France; Robert Debré Hospital; Servicio Madrileño de Salud, Madrid, Spain; St George's, University of London; SYNAPSE Research Management Partners S.L; Therakind limited; University of Edinburgh; University of Liverpool; University of Tartu
• Treatments: Vancomycin

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