External Validation of the Beta-lactam Target Non-attainment (BATMAN) Risk Score in Adult ICU Patients: a Diagnostic Multivariate Predictive Risk Model (BATMAN)

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.

Study Overview

• Status: Recruiting
• Conditions: Infection, Bacterial; Beta-lactam Antibiotics; Critical Care; Risk Model; Therapeutic Drug Monitoring

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.

• Study Type: Observational
• Enrollment (Estimated): 130

Contacts and Locations

• Study Contact: Name: Chantal Kats, MSc; Phone Number: +31634424848; Email: c.kats@haaglandenmc.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3582 KE
    • Not yet recruiting
    • Diakonessenhuis
    • Contact: Attila Karakus, MD
    • Principal Investigator: Attila Karakus, MD
  • Gelderland
    • Zwolle, Gelderland, Netherlands, 8025 AB
      • Not yet recruiting
      • Isala Hospital
      • Contact: Jasper Haringman, MD
      • Principal Investigator: Jasper Haringman, MD
      • Sub-Investigator: André Wieringa, MSc
  • Limburg
    • Venlo, Limburg, Netherlands, 5912 BL
      • Recruiting
      • Viecuri Medical Center
      • Contact: Manon Fleuren-Janssen
      • Principal Investigator: Manon Fleuren-Janssen
  • South-Holland
    • Rotterdam, South-Holland, Netherlands, 3015 GD
      • Recruiting
      • Erasmus Medical Center
      • Contact: Alan Abdulla, PhD, MD
      • Principal Investigator: Alan Abdulla, PhD, MD
      • Sub-Investigator: Nicole Hunfeld, PhD, MD
      • Sub-Investigator: Rik Endeman, PhD, MD
    • Rotterdam, South-Holland, Netherlands, 3045 PM
      • Not yet recruiting
      • Franciscus Gasthuis & Vlietland
      • Contact: Dorien Kiers, MD
      • Principal Investigator: Dorien Kiers, MD
    • The Hague, South-Holland, Netherlands, 2512VA
      • Not yet recruiting
      • Haaglanden Medisch Centrum
      • Contact: Chantal Kats, MSc
      • Principal Investigator: Peter Van Vliet, PhD, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Discrimination	The discrimination of the diagnostic risk score will be displayed in the concordance index (c-index), which is identical to the area under the receiver operating curve (AUROC), where the true positive rate (y-axis) will be plotted against the false positive rate (x-axis).	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.
Calibration	The calibration of the risk score will be assessed with a calibration plot, where the average predicted risk of target non-attainment is compared with the overall event rate of target non-attainment.	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative predictive value	The ratio of subjects truly diagnosed as negative (target attainment) to all those who had negative test results	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.
Positive predictive value	The ratio of subjects truly diagnosed as positive (target non-attainment) to all those who had positive test results.	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.
Sensitivity	Sensitivity is the percentage of true positives.	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.
Specificity	Specificity is the percentage of true negatives.	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.
Misclassification	Percentage of observations that were incorrectly predicted (false negatives and false positives)	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.

Collaborators and Investigators

• Sponsor: Chantal Kats
• Investigators: Principal Investigator: Alan Adulla, PhD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): October 1, 2023
• Study Completion (Estimated): November 1, 2023

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 15, 2022

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Therapeutic drug monitoring; Critical care; External validation; Risk model; Beta-lactam antibiotics; infections, bacterial
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: NL181245.078.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No