In neonatal population wide inter-and intra-individual variability of pharmacokinetics makes extremely difficult to ensure optimal exposure of vancomycin with standard regimens. On average >50% of baseline drug concentrations are out of target (10-15 mg/l) range and empiric dose adjustment does not improve the results sufficiently. Model-based initial dosage with Bayesian individual dose adjustment seems to be a promising method for improving vancomycin dosing accuracy in neonatal population.
Conditions
Interventions
Trade Name: Vancosan 500 mg
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
Sponsors
Tartu University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject inclusion criteria 1. Postnatal age (PNA) =72 hours and = 90 days at the beginning of vancomycin therapy 2. Vancomycin treatment is indicated at the discretion of the attending physician 3. Informed consent signed by parent or guardian (prospective intervention group) and/or Ethics and Data protection committee approval in place. 4. Patient does not participate in other "device"-studies Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subject exclusion criteria 1. Not expected to survive over 72 hours from initiation of vancomycin treatment 2. No informed consent given (if recruiting to DosOpt study group) 3. Current participation in competitive study, what takes blood tests for research purposes.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective • To evaluate the validity (accuracy and variability) of vancomycin dosing in neonates with the free software DosOpt to determine whether individual dose optimization gives an advantage over empirical dosing. ;Secondary Objective: Secondary objective • To demonstrate the safety of dose adjustment with DosOpt in neonates • To analyze the impact of each additional TDM measurement to the prediction accuracy and variability in order to give recommendations on TDM routines in neonates • To describe the outliers: which demographic features (i.e. PMA, CW, small for gestational age (SGA)) and concomitant diseases (i.e. renal and circulatory status) degrade the prediction capability the most. • To describe the patients (i.e PMA, CW, concomitant diseases) who get the most benefit from adjusting dose with DosOpt. • To analyze the effect of protein and albumin levels on DosOpt prediction accuracy • To get a real work experience with DosOpt and improve the DosOpt user interface. ;Primary end point(s): Primary endpoint The proportion of neonates attaining the narrow trough concentration target range Ctr 10-15 mg/L and clinically accepted target range Ctr 10-20mg/l in the two study arms (PTA%Ctr 10-15/ Ctr 10-20= probability of target attainment) ;Timepoint(s) of evaluation of this end point: Every time then trough concentration are measured (every dose adjustment visits, usually after 36-48h) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint (only for DosOpt group) 1. The proportion of neonates, attaining the PD target of AUC/MIC= 400 and =700 (PTA% AUC/MIC 400-700) 2. Clinical cure, defined as: reinfection, new infection, microbiologic cure (time to sterile blood culture), time to CRV normalization. 3. Safety endpoints include : a. The description of all adverse events (AE) experienced by infants receiving study drugs. Clinical and laboratory AE will be recorded until the end of therapy (EOT) and follow up visits (7 days after the end of therapy) and graded according to the need for a specific medical intervention b. Incidence of acute kidney injury (AKI): defined by modified neonatal KDIGO criterias (renal function parameters: diuresis, creatinine, urea, cystatin C will be used) c. Ototoxicity: otoacoustic emission (OAE) will be documented from the medical history afterwards. Hearing screening (OAE) should be performed after 34weeks PMA according to local, neonatal hearing screening guidelines. 4. Practical implementation endpoints include: a. Identification, discription and documentation of all errors related to the use of DosOpt in clinical practise and detect the possible sources of errors. ;Timepoint(s) of evaluation of this end point: 1. Each dose adjustment visit 2. From the start of recruitment until 7 days after treatment (follow up vist) 3a and 3b From recruitment (V0) to the 7 day follow up vist (V7p) 3c OAE visit- then hearing screening is performed (depends on child and neonatal unit) 4a- Each dose optimization visit (from V0-Vn), there n- is the last visit of dose adjustment | — |
Countries
Estonia
Contacts
Public ContactPediatric Intensive Care Unit
Anaesthesiology and Intensive Care Clinic
Outcome results
None listed