NeoVanc - Vankomütsiin hilise sepsise ravis - optimaalne ravirežiim
The key objective of the NeoVanc to develop an optimal dosing and monitoring regimen for vancomycin use in preterm neonates and infants under 3 months of age and then to conduct a PK/PD based randomised clinical trial with PK/PD targets as the primary outcome. In addition, the efficacy and safety of different dosing regimens will be described. An age-appropriate formulation (a new 125 mg vial) will be investigated in the clinical trial as recommended by the PDCO in the provisional PIP 120-day feedback. Gender and age subgroups will be accounted for in the PK models used to define the optimal dosage regimen and in the design and analysis of the clinical trial. The clinical strategy is based on an innovative PK/PD bridging strategy in which two different dosing regimens of vancomycin will be directly compared to each other. The most appropriate PD endpoint (most likely AUC/MIC) for CoNS will be evaluated and defined in the experimental pre-clinical animal studies, combined with a detailed population PK meta-analysis. The pre-clinical studies defining the optimal PK/PD target will be taken forward to the randomised clinical trial. The specific objectives will be: i) to define the preclinical PK/PD relationships for vancomycin against clinically relevant Gram positive pathogens in hollow fibre infection and laboratory animal models and bridge the results to human neonates (NeoVanc1) ii) to conduct a population PK meta-analysis of all available neonatal vancomycin data and define in collaboration with NeoVanc 1, a new optimal vancomycin dosing regimen (NeoVanc2) iii) to compare a new improved “Optimal” vancomycin dosing regimen with an accepted European standard of care regimen in a Phase II RCT in terms of efficacy and safety (NeoVanc3) The NeoVanc study will act to further development of the experienced European neonatal infection research network, facilitating the development of future clinical trials in novel antimicrobials as they progress through the EMA regulatory processes. In Estonia clinical trial will be conducted in the University Clinics of Tartu and Tallinn Children’s Hospital. We aim to recruit 40 patients in clinical study NeoVanc2. UTartu is a leading partner in that clinical study.