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

Burn Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01965340
• Other study ID #: Protocol 195/13
• Status: Completed
• Phase: N/A
• First received: September 27, 2013
• Last updated: November 10, 2016
• Start date: October 2013
• Est. completion date: October 2016

Study information

• Verified date: November 2016
• Source: University of Lausanne Hospitals
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial Summary

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 Burn shock and respiratory failure that used to be the major cause of mortality have progressively been replaced by sepsis and multiple organ failure.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Burn

Intervention

Other:
• Systematic Therapeutic Drug Monitoring for the intervention group

Locations

Country	Name	City	State
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud

Sponsors (1)

Lead Sponsor	Collaborator
University of Lausanne Hospitals

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time required to achieve anti-infective plasma concentrations in the target		Up to 3 years	Yes
Primary	Numbers of concentrations within the target during an anti-infective agents course		Up to 3 years	Yes
Secondary	Anti-infective agents consumption		Up to 3 years	No
Secondary	Development of antibiotic resistance		Up to 3 years	Yes
Secondary	Length of ICU stay based on TBSA		Up to 3 years	No
Secondary	Characterization of the pharmacokinetic profile of most widely used antibiotics		Up to 3 years	No
Secondary	Concentration - efficacy analysis	Population pharmacokinetic (NONMEM software)	Up to 3 years	No
Secondary	Failure / resolution rate of infectious episodes		Up to 3 years	Yes
Secondary	Concentration - toxicity analysis	Population pharmacokinetic (NONMEM software)	Up to 3 years	Yes