Impact of Therapeutic Drug Monitoring on Anti-Infective Agents Amongst Severely Burned Patients Requiring ICU Admission

Sepsis is the major cause of morbidity and mortality amongst burn patients. Burn shock and respiratory failure that used to be the major cause of mortality have progressively been replaced by sepsis and multiple organ failure. It is not rare that treatment failures occurs several weeks, or even months after injury as a consequence of sepsis usually caused by multi-drug resistant (MDR) microorganisms. Introduction of early surgery combined with topical and systemic antibiotherapy dramatically enhanced survival from sepsis after burn trauma, but further improvement is impaired by the rapid development of hard-to-treat MDR bacteria.

Correct prescription of anti-infective agents could be one way to curb the steadily increasing development of multidrug resistance. Administration of antibiotic to burn patient is complex: they frequently suffer from kidney dysfunction, they usually experience tremendous shifts of liquids between intra-vascular - inter-cellular and intra-cellular compartments, they often are hypo-albumin and protein-emic, and finally they present with a profoundly modified metabolism. All those aspects make this particular population of patients at high risk of both under or over prescription.

Monitoring of drug concentrations in the plasma of patients, so-called TDM for Therapeutic Drug Monitoring, has been introduced to clinical practice for several decades primarily to avoid toxicity of a small number of drugs with narrow therapeutic windows. However, with the increasing availability of detection techniques, the number of drugs that can be measured in the plasma of patients has grown tremendously over the last decade. As a consequence, it is currently possible to monitor drug concentrations not only to prevent toxicity, but also to improve efficacy. For instance, several studies demonstrated that TDM improved antibiotic prescription in different populations of hospitalized patients, including critically ill patients, with a direct impact on outcome.

Such studies amongst burn patients are however lacking, although this particular population is at high risk to suffer from mis-prescription. We thus hypothesize that systematic TDM could improve antibiotic prescription in this peculiar population. To this end, we propose to implement a 3-year prospective, randomized, mono-centric, clinical trial that will analyze the impact of systematic TDM on anti-infective agent prescription amongst burned patients.

Study Overview

• Status: Completed
• Conditions: Burn
• Intervention / Treatment: Other: Systematic Therapeutic Drug Monitoring for the intervention group

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• All adult burn patients (≥ 18 years) admitted to the University Hospital of Lausanne during the study period receiving systemic anti-infectives agents for which TDM is available will be included.

Exclusion Criteria:

• Patients not receiving systemic anti-infective agents therapy
• Patients with length of hospital stay <72 hours
• Patients refusing to give their written consent (or for which the therapeutic representative refuses) or incapable of understanding and lack of legal representative
• Pregnant or breastfeeding women
• Children <18 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with systematic TDM of anti-infective agents; Patients with systematic TDM of anti-infective agents and dosages adapted accordingly	Other: Systematic Therapeutic Drug Monitoring for the intervention group
No Intervention: Patients treated as usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time required to achieve anti-infective plasma concentrations in the target	Up to 3 years
Numbers of concentrations within the target during an anti-infective agents course	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-infective agents consumption		Up to 3 years
Development of antibiotic resistance		Up to 3 years
Length of ICU stay based on TBSA		Up to 3 years
Characterization of the pharmacokinetic profile of most widely used antibiotics		Up to 3 years
Concentration - efficacy analysis	Population pharmacokinetic (NONMEM software)	Up to 3 years
Failure / resolution rate of infectious episodes		Up to 3 years
Concentration - toxicity analysis	Population pharmacokinetic (NONMEM software)	Up to 3 years

Collaborators and Investigators

• Sponsor: University of Lausanne Hospitals

Publications and helpful links

General Publications

• Fournier A, Goutelle S, Que YA, Eggimann P, Pantet O, Sadeghipour F, Voirol P, Csajka C. Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center. Antimicrob Agents Chemother. 2018 Aug 27;62(9):e00505-18. doi: 10.1128/AAC.00505-18. Print 2018 Sep.
• Fournier A, Eggimann P, Pantet O, Pagani JL, Dupuis-Lozeron E, Pannatier A, Sadeghipour F, Voirol P, Que YA. Impact of Real-Time Therapeutic Drug Monitoring on the Prescription of Antibiotics in Burn Patients Requiring Admission to the Intensive Care Unit. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e01818-17. doi: 10.1128/AAC.01818-17. Print 2018 Mar.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: September 27, 2013
• First Submitted That Met QC Criteria: October 17, 2013
• First Posted (Estimate): October 18, 2013

Study Record Updates

• Last Update Posted (Estimate): November 11, 2016
• Last Update Submitted That Met QC Criteria: November 10, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: patients
• Other Study ID Numbers: Protocol 195/13