InfectionPhase 1NCT03481569
Population Pharmacokinetic-pharmacodynamic (PK-PD) Study of 9 Broad-Spectrum Anti-infective Agents in the Cerebro Spinal Fluid (CSF) of Brain Injured Patients With an External Ventricular Drainage (EVD).
A Phase 1 study testing Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine use in people with Infection, run by Poitiers University Hospital at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection
- What is being tested?
- Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine use
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 1 siteFrance
- Study dates
- 6 Jul 2018to 6 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 or no emergency procedure for continuous infusion antibiotic 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
Trial locations and contacts
1 site in 1 country.
About this study
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 8 ATB indicated in CNS infections (vancomycin, daptomycin, ceftazidime, meropenem, colistin, linezolid, piperacillin-tazobactam and ceftaroline) and to study the Cefepime diffusion in the CSF, known to be highly neurotoxic.
- Conditions
- Infection
- Being tested
- Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine use
- Medical subject headings
- Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine useOther
Blood and cerebrospinal fluid pharmacocinetic samples at different time point
| Study group | Role | What they receive |
|---|---|---|
| Pharmacokinetic sample | Experimental | Plasma and cerebrospinal fluid samples performed at different timepoint during administration of antibiotic prescribed in routine use Receives: Other: Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine use |
What is being measured
The primary outcome is the main question the study is designed to answer.
CSF-to-plasma area under the unbound concentration-time curve for each antibiotic
Measured: 5 days
Secondary outcomes (3)
Time > Minimal Inhibitrice Concentration for each antibiotic
Measured: 5 days
Area Under the Curve / Minimal Inhibitrice Concentration for each antibiotic
Measured: 5 days
Peak concentration / Minimal Inhibitrice Concentration for each antibiotic
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start6 Jul 2018
- Primary completion6 Jul 2023
- Study completion6 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfectionStudies of the same condition, open and under way.
- More trials run by Poitiers University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Pharmacokinetic study
- Masking
- None (open label)
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Lead sponsor
- Poitiers University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03481569
- Sponsor's protocol ID
- PKpop LCR
- Status last verified
- Jul 2023
- First submitted
- 21 Mar 2018
- Last updated
- 10 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetic-pharmacodynamic (PK-PD) Study of 9 Broad-Spectrum Anti-infective Agents in the Cerebro Spinal Fluid (CSF) of Brain Injured Patients With an External Ventricular Drainage (EVD).
- ClinicalTrials.gov ID
- NCT03481569
- Acronym / sponsor ID
- PKpop LCR
- Conditions
- Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- Poitiers University HospitalUniversity, hospital or other
- Study start
- 6 Jul 2018 (actual)
- Primary completion
- 6 Jul 2023 (actual)
- Study completion
- 6 Jul 2023 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 8 ATB indicated in CNS infections (vancomycin, daptomycin, ceftazidime, meropenem, colistin, linezolid, piperacillin-tazobactam and ceftaroline) and to study the Cefepime diffusion in the CSF, known to be highly neurotoxic.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Pharmacokinetic study
| Arm | Type | Receives |
|---|---|---|
| Pharmacokinetic sample | Experimental | Other: Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine usePlasma and cerebrospinal fluid samples performed at different timepoint during administration of antibiotic prescribed in routine use |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- 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 or no emergency procedure for continuous infusion antibiotic signed
- Patients not benefiting from a Social Security scheme or not benefiting from it through a third party
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine useBlood and cerebrospinal fluid pharmacocinetic samples at different time point | Other | Pharmacokinetic sample |
Primary outcome
CSF-to-plasma area under the unbound concentration-time curve for each antibiotic
Time frame: 5 days
3 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Blood and cerebrospinal fluid pharmacocinetic samples on one of the nine antibiotics prescribed in routine use in people with Infection, run by Poitiers University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CSF-to-plasma area under the unbound concentration-time curve for each antibiotic (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2023.