Clinical trial NCT05542771: External Validation of the Beta-lactam Target Non-attainment (BATMAN) Risk Score in Adult ICU Patients: a Diagnostic Multivariate Predictive Risk Model
Official title: External Validation of the Beta-lactam Target Non-attainment (BATMAN) Risk Score in Adult ICU Patients: a Diagnostic Multivariate Predictive Risk Model
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Infection, Bacterial
Beta-lactam Antibiotics
Critical Care
Risk Model
Therapeutic Drug Monitoring
Keywords: External validation
Critical care
Risk model
Beta-lactam antibiotics
Therapeutic drug monitoring
infections, bacterial
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2022-09-15
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All adult patients admitted to the adult general ICU wards and treated with the target antibiotics who meet the inclusion criteria will be included.

Brief summary: Intensive care (IC) patients regularly get infections. Sometimes it is even the reason of admission to the intensive care unit. To treat these infections, we give medicines called antibiotics, such as β-lactams antibiotics. Every IC patient receives the same dose of β-lactams antibiotics, while we know this can lead to undertreatment in some IC patients. The BATMAN risk score was created to predict which IC patient is undertreated. This study aims to validate the BATMAN risk score so it can be used in clinical practice.

Detailed description: In order to predict which intensive care unit (ICU) patients are not likely to achieve target attainment of beta-lactam antibiotics, a diagnostic multivariable prediction model was developed using random forest analysis. Gender, age, creatinine, and type of beta-lactam antibiotic were included in the final model and translated into a user-friendly and easy-to-implement risk score. As the name suggests, the beta-lactam target non-attainment (BATMAN) risk score predicts which adult ICU patients fail to achieve target attainment and intents efficient use of TDM of beta-lactam antibiotics. In order to use the BATMAN risk score in as many hospitals as possible in clinical practice, an external validation will be performed by a multicenter prospective observational study. All adult ICU patients admitted to the participating hospitals that are treated with beta-lactam antibiotics will be screened for eligibility. One beta-lactam trough plasma concentration, clinical and non-clinical data will be collected prospectively. To our knowledge, no other beta-lactam target non-attainment risk score for adult ICU patients has yet been developed let alone externally validated. This research is essential because ICU patients are a highly heterogenic group of patients that undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics, such as beta-lactam antibiotics. For the beta-lactams, achievement of an adequate drug level is associated with a higher likelihood of clinical success and a decrease in the potential for antimicrobial resistance. Yet, target attainment remains a challenge with the traditional 'one-dose-fits-all' strategy.

Eligibility criteria: Inclusion criteria:

* Written informed consent has been obtained from the patient or their legally authorised representative
* Age ≥18 years
* Treated with one of the following beta-lactam antibiotics at the ICU with intermitted dosage

  * Amoxicillin (with or without clavulanic acid)
  * Cefotaxime
  * Ceftazidime
  * Cefuroxime
  * Flucloxacillin
  * Meropenem
  * Piperacillin with tazobactam
* Eligible blood material within 36 hours after start of beta-lactam antibiotic to determine target attainment (100%ƒT \> MICECOFF).
* Suitable intravenous/intra-arterial access to facilitate sample collection

Exclusion Criteria:

* Pregnancy
* Beta-lactam antibiotic cessation before blood sample collection
* Receiving beta-lactam antibiotic only as prophylaxis within the context of Selective Digestive tract Decontamination (SDD)
* Patients with renal replacement therapy
* Patients with burn injury

Primary outcomes:
measure: Discrimination
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
measure: Calibration
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
Secondary outcomes:
Other outcomes:
measure: Negative predictive value
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
measure: Positive predictive value
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
measure: Sensitivity
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
measure: Specificity
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
measure: Misclassification
timeFrame: Target attainment prediction based on the BATMAN risk score is calculated with patient data within 36 hours after of start therapy. Target attainment based on serum levels are based are measured within 36 hours after start of therapy.
Locations:
city: Zwolle
country: Netherlands
facility: Isala Hospital
state: Gelderland
city: Venlo
country: Netherlands
facility: VieCuri Medical Center
state: Limburg
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: South-Holland
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
state: South-Holland
city: The Hague
country: Netherlands
facility: Haaglanden Medisch Centrum
state: South-Holland
city: Utrecht
country: Netherlands
facility: Diakonessenhuis
Study officials:
affiliation: Erasmus Medical Center
name: Alan Adulla, PhD
role: PRINCIPAL_INVESTIGATOR
References: