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Trial record 3 of 257 for:    Anti-Infective Agents AND Antibiotics, Antitubercular AND broad

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 4, 2019
Sponsor:
Information provided by (Responsible Party):
Poitiers University Hospital

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 175 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Pharmacokinetic study
Masking: None (Open Label)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. CSF-to-plasma area under the unbound concentration-time curve for each antibiotic [ Time Frame: 5 days ]

Secondary Outcome Measures :
  1. Time > Minimal Inhibitrice Concentration for each antibiotic [ Time Frame: 5 days ]
  2. Area Under the Curve / Minimal Inhibitrice Concentration for each antibiotic [ Time Frame: 5 days ]
  3. Peak concentration / Minimal Inhibitrice Concentration for each antibiotic [ Time Frame: 5 days ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Brain injury patients requiring intensive care management with external ventricular drainage
  • Age ≥18 years old
  • Patient with a CNS or other site infection treated with one or several of the ATB of the study
  • Signed informed consent of the patient or the close friend / family after giving a clear and loyal information about the study
  • Free subject, without guardianship or curatorship or subordination
  • Patients benefiting from a Social Security system or benefiting from it through a third party

Exclusion Criteria:

  • Age under 18 years old
  • Acute renal failure defined with a creatinine clearance < 50 mL/min and / or under continuous haemodialysis
  • Contraindication to the antibiotic studied
  • No informed consent signed
  • Patients not benefiting from a Social Security scheme or not benefiting from it through a third party
  • Persons benefiting from enhanced protection, namely minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social institution, adults under legal protection, and finally patients in emergencies.
  • Pregnant or nursing women

Information from the National Library of Medicine

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


Contacts
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Contact: Claire DAHYOT-FIZELIER +33(0)549444840 claire.dahyot-fizelier@chu-poitiers.fr
Contact: Nadia IMZI +33(0)549443357 nadia.imzi@chu-poitiers.fr

Locations
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France
CHU of Poitiers Recruiting
Poitiers, France, 86000
Contact: Nadia IMZI         
Principal Investigator: Claire DAHYOT-FIZELIER, MD         
Sponsors and Collaborators
Poitiers University Hospital

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Responsible Party: Poitiers University Hospital
ClinicalTrials.gov Identifier: NCT03481569     History of Changes
Other Study ID Numbers: PKpop LCR
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anti-Bacterial Agents
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents