Population Pharmacokinetic-pharmacodynamic (PK-PD) Study of 7 Broad-Spectrum Anti-infective Agents in the Cerebro Spinal Fluid (CSF) of Brain Injured Patients With an External Ventricular Drainage (EVD).
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|ClinicalTrials.gov Identifier: NCT03481569|
Recruitment Status : Recruiting
First Posted : March 29, 2018
Last Update Posted : July 5, 2019
Nosocomial Central Nervous System infections are difficult to treat and an early appropriate therapy can improve prognosis. The two main reasons for treatments failure are the difficulty to reach high concentrations of antibiotics (ATB) in CNS because of brain barriers (BB), and the emergence of Multi-Drug-Resistant (MDR) pathogens that require high ATB concentrations for being killed. Therefore a better knowledge of ATB CNS distribution and PK-PD characteristics is essential for efficiency of treatments and to avoid resistance progression. Because of BB and cerebrospinal fluid (CSF) turnover, unbound (active) concentrations of ATB in CSF are frequently much lower than corresponding plasma concentrations, which therefore may not be used to predict efficacy. However except for patients with EVD, CSF access is difficult. Overall the litterature about ATB distribution within CSF exist but PK-PD publications are rarer. Especially for Broad Spectrum ATB which are recommended in case of invasive infection in ICU patients due to MDR pathogens such as Acinetobacter baumanii, extended spectrum ß-Lactamase producing (ESBL) pathogens or Multiresistant Staphylococcus aureus.
Furthermore, measuring ATB concentrations within the CSF at certain time-points is necessary but not sufficient to predict antimicrobial efficacy. First PK modelling is required to describe the full CSF concentrations versus time profiles. Then targets must be obtained from literature or determined for the relevant PD index, which may be, depending of the antibiotic, Time over Minimal Inhibitrice Concentration (T>MIC), Area Under the Curve over MIC (AUC/MIC) or peak concentration over MIC (Cmax/MIC). Eventually Monte-Carlo simulations can be conducted to predict the probability of target attainment according to various dosing regimens to find the optimal one.
The goal of this multicenter population PK-PD study is to characterize CSF distribution and challenge recommended dosing regimens of 7 ATB indicated in CNS infections (vancomycin, daptomycin, ceftazidime, meropenem, colistin, aztreonam, linezolid).
|Condition or disease||Intervention/treatment||Phase|
|Infection||Other: Blood and cerebrospinal fluid pharmacocinetic samples on one of the seven antibiotics prescribed in routine use||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||175 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Pharmacokinetic study|
|Masking:||None (Open Label)|
|Official Title:||Population Pharmacokinetic-pharmacodynamic (PK-PD) Study of 7 Broad-Spectrum Anti-infective Agents in the Cerebro Spinal Fluid (CSF) of Brain Injured Patients With an External Ventricular Drainage (EVD).|
|Actual Study Start Date :||July 6, 2018|
|Estimated Primary Completion Date :||July 2020|
|Estimated Study Completion Date :||October 2020|
Experimental: Pharmacokinetic sample
Plasma and cerebrospinal fluid samples performed at different timepoint during administration of antibiotic prescribed in routine use
Other: Blood and cerebrospinal fluid pharmacocinetic samples on one of the seven antibiotics prescribed in routine use
Blood and cerebrospinal fluid pharmacocinetic samples at different time point
- CSF-to-plasma area under the unbound concentration-time curve for each antibiotic [ Time Frame: 5 days ]
- Time > Minimal Inhibitrice Concentration for each antibiotic [ Time Frame: 5 days ]
- Area Under the Curve / Minimal Inhibitrice Concentration for each antibiotic [ Time Frame: 5 days ]
- Peak concentration / Minimal Inhibitrice Concentration for each antibiotic [ Time Frame: 5 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03481569
|Contact: Claire DAHYOT-FIZELIER||+33(0)firstname.lastname@example.org|
|Contact: Nadia IMZI||+33(0)email@example.com|
|CHU of Poitiers||Recruiting|
|Poitiers, France, 86000|
|Contact: Nadia IMZI|
|Principal Investigator: Claire DAHYOT-FIZELIER, MD|