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

NCT01965340 | Completed DMC

• 1 other identifier: Protocol 195/13
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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 Burn shock and respiratory failure that used to be the major cause of mortality have progressively been replaced by sepsis and multiple organ failure.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

Conditions

Burn

Keywords

patients

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

  Up to 3 years

Study Arms (2)

Patients with systematic TDM of anti-infective agents

EXPERIMENTAL

Patients with systematic TDM of anti-infective agents and dosages adapted accordingly

Other: Systematic Therapeutic Drug Monitoring for the intervention group

Patients treated as usual

NO INTERVENTION

Interventions

Systematic Therapeutic Drug Monitoring for the intervention group OTHER

Patients with systematic TDM of anti-infective agents

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Lausanne Hospitals: lead

Study Sites (1)

Centre Hospitalier Universitaire Vaudois

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 29914948 DERIVED

• 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.

  PMID: 29263079 DERIVED

MeSH Terms

Conditions

Burns

Condition Hierarchy (Ancestors)

Wounds and Injuries

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Anne Fournier

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 18, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: November 11, 2016

Record last verified: 2016-11

Locations

CH (1)