The aim of this study is to describe the PK/PD characteristics of frequently used beta-lactam antibiotics in PICU patients. The main objective is to identify whether current antibiotic dosing regimens of the selected beta-lactams achieve defined…
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Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
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Intervention
Outcome measures
Primary outcome
The PK/PD endpoints are the unbound concentration above the MIC at 100% (PICU
target) of the dosing interval (*T*>*MICECOFF and *T*>*4 x MICECOFF). The
percentage *T*>*MIC is determined by calculating the intercept of the MIC
values with the concentration-time curve.
The following PK/PD indices are calculated:
• %*T>MICECOFF for each individual patient
• % of patients that achieved the target of 100% *T>MICECOFF and 100%
*T>4×MICECOFF
• Target attainment for the study antibiotics and dosing regimens to reach the
target of 100% *T*>*MIC and 100% *T*>*4×MIC for a range of MICs (0.03125 to 128*
mg/L)
Secondary outcome
Secondary endpoints are estimated multivariate binomial and binary logistic
regression models, to examining the association of target attainment with
patient characteristics and clinical outcomes. We defined ICU length of stay
(LOS) from the start of therapy (enrollment) as a secondary endpoint. Factors
likely to contribute to these two outcomes were analyzed for association based
on clinical relevancy and previously described relationships (11). These
included patient characteristics (age, gender, body mass index (BMI)), organ
dysfunction score (PELOD), serum albumin, serum urea, sepsis, estimated
glomerular filtration rate (eGFR >= 90 mL/min/1.73 m2), and presence of
extracorporeal circuits (CRRT (continuous renal replacement therapy), ECMO
(extracorporeal membrane oxygenation)).
Background summary
Morbidity and mortality in critically ill patients with infection is a global
health problem. Emerging evidence supports the importance of optimized
antibiotic exposure in pediatric intensive care unit (PICU) patients, while
evidence based antibiotic dosing in PICU patients in clinical practice is
limited. Changes in pharmacokinetic (PK) parameters of antibiotics in
subpopulations of critically ill patient have been defined in previous studies.
However, there are no data from studies assessing whether the issues identified
in a controlled research environment correspond to clinical practice.
Assessment of pharmacodynamic target attainment is warranted to identify
whether clinical outcomes for patients admitted to the PICU can be improved. We
propose an exploratory pharmacokinetic and pharmacodynamic (PK/PD) study to
analyse whether current antibiotic dosing regimens of frequently used beta
lactam antibiotics achieve defined therapeutic target concentrations in PICU
patients.
Study objective
The aim of this study is to describe the PK/PD characteristics of frequently
used beta-lactam antibiotics in PICU patients. The main objective is to
identify whether current antibiotic dosing regimens of the selected
beta-lactams achieve defined therapeutic target concentrations, within the
first 36 hours after start of therapy in PICU patients.
Study design
The design is a multicenter, prospective, observational pharmacokinetic and
pharmacodynamic study.
Study burden and risks
With the exception of obtaining blood samples, there is no burden or risk
associated with participating in this study. Risks are low and burden is
minimal.
's Gravendijkwal 230
Rotterdam 3000 CA
NL
's Gravendijkwal 230
Rotterdam 3000 CA
NL
Listed location countries
Age
Inclusion criteria
All patients admitted to the pediatric intensive care unit wards and given
standard of care intravenous therapy of target antibiotic are screened for
participating trial.
Antibiotic initiation based on clinical suspicion of infection and/or cultured
pathogens susceptible to the target drugs, initial dosage prescription, and
duration of therapy are at the discretion of the attending physician. In order
to be eligible to participate in this study a subject must also meet all the
followinng criteria:
• Written informed consent has been obtained from the patient or their legally
authorized representative.
• Recruitment within 36 hours after start of antibiotic therapy
• Intravenous antibiotic therapy of the target antibiotic should be aimed for
at least 2 days.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• Premature infants
• History of anaphylaxis for the study antibiotics
• Consent not obtained
• Study antibiotic cessation before blood collection
• Prophylactic use of the study antibiotics
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL76194.078.21 |