The aim of this trial is to evaluate a new early dosage adjustment strategy (TDM) of beta-lactam and fluoroquinolones in adult ICU patients to achieve the adequate pharmacodynamic targets (PDT), compared to the usual treatment strategy.
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Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome parameter is the length of ICU stay (LOS).
The cohort COVID-19 patients are analysed as a separate subpopulation.
Furthermore, to rule out any additional effects of continuous infusion on the
endpoints, we will also consider this population as a separate cohort. This
applies to all endpoints, and for primary endpoint the difference in achieving
the pharmacodynamics targets (delta target attainment) is determined instead of
the LOS in the both the COVID-19 and continuous infusion cohorts. The LOS is
determined in both cohorts, but is reported as a secondary outcome measure.
The target for continuous infusion is increased from 100% *T> MICECOFF to 100%
*T> 4xMICECOFF, with the dose reduction threshold for intermittent and
continuous infusion being equal (10xMICECOFF).
Secondary outcome
Secondary aims are to show that active TDM results in improved clinical
outcome, increased cost-effectiveness, better quality of life.
Clinical outcomes are 28-day mortality, decrease in SOFA (sequential organ
failure assessment score), and hospital stay. Cost-effectiveness will be
determined intramural and extramural and using appropriate health * economic
analysis. Furthermore, the number of antibiotic days, use of other antibiotics,
and decrease in CRP and procalcitonin will be registered. At last, major side
effects will be reported.
Quality of life will be measured 6 months after ICU stay, as a proxy for
post-ICU syndrome.
Amendment April 2020 secondary outcome measures:
* Change from baseline in white blood cell and differential count [T=0-28].
From routine blood tests.
* Time to first negative in 2019 novel Corona virus RT-PCR test [T=0-28]. From
routine swabs tests.
Background summary
Emerging evidence supports the importance of optimized antibiotics exposure in
intensive care unit (ICU) patients, while evidence based antibiotic dosing in
ICU 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 is essential in order to determine whether
actions, such as the use of therapeutic drug monitoring (TDM), are required to
change our existing antibiotic prescribing practices in ICU patients. The
potential benefits of a TDM-based approach include a better outcome because of
more appropriate antibiotic concentrations, but also less resistance
development and avoidance of toxicity. It is most commonly used when the PK and
therefore the optimal dose of a drug for an individual patient are difficult to
predict. In clinical practice, this approach has been routinely used for many
years for vancomycin and aminoglycosides. However, expansion of this practice
to cephalosporin and fluoroquinolone antibiotics, which are frequently used to
treat infections in critically ill patients, has not been widely tested as a
routine intervention. This is very unfortunate, because the contemporary
antibiotic dosing is debatable in severely ill patients as most dosing
references have been derived from studies that do not consider the occurrence
of pathophysiological changes in critical illness.
Study objective
The aim of this trial is to evaluate a new early dosage adjustment strategy
(TDM) of beta-lactam and fluoroquinolones in adult ICU patients to achieve the
adequate pharmacodynamic targets (PDT), compared to the usual treatment
strategy.
Study design
The design is a multicenter, prospective, randomised trial: active TDM versus
non-TDM group of beta-lactam and fluoroquinolone antibiotics.
Intervention
Antibiotic start dosing will occur as deemed by the ICU clinician and/or
infectious disease clinician and the local dosing practices. Assigned
interventions in the active TDM group: dosage of beta-lactam and
fluoroquinolone antibiotics will be adjusted according to serum concentrations.
In the non-TDM (control) group samples of serum concentrations of beta-lactam
and fluoroquinolone will be collected for comparison. The antibiotic
concentrations in the control group will be measured in bulk later and blinded
for the ICU clinician and/or infectious disease clinician.
Study burden and risks
With the exception of blood collection, there is no discomfort associated with
participation in this study. Risks are moderate and the 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 adult general ICU wards and given standard of care
intravenous therapy of the target antibiotic are screened for participating in
trial.
Patients will be admitted to the cohorts based upon the following three cohorts:
1. Main cohort (COVID-19 Negative, No continuous infusion)
2. COVID-19 cohort (including continuous infusion)
3. Continuous infusion cohort (COVID-19 Negative)
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
of the following criteria:
* *18 years of age
* Receiving intravenous antibiotic therapy of the target drugs (including
continuous infusion)
* Treatment should be aimed for at least 2 days.
* Written informed consent has been obtained from the patient or their legally
authorized representative.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
* Pregnancy
* Patient already enrolled in this trial
* Antibiotic cessation before sampling
* Medium care and burn wound patients admitted to the ICU
* Patients receiving target antibiotics only as prophylaxis within the context
of Selective Digestive tract Decontamination (SDD)
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 |
|---|---|
| EudraCT | EUCTR2017-004677-14-NL |
| CCMO | NL64070.078.17 |