Therapeutic Drug Monitoring of Anti-infectious Drugs in Intensive Care Unit

Infection, Bacterial Clinical Trial

— STP-ATB-REA  

Official title:

Evaluation of the Use of Therapeutic Drug Monitoring in the Management of Infections in Intensive Care Unit Patients.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03339869
• Other study ID #: 2017-05
• Status: Not yet recruiting
• Phase: N/A
• First received: November 8, 2017
• Last updated: November 10, 2017
• Start date: January 2, 2018
• Est. completion date: October 31, 2020

Study information

• Verified date: November 2017
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Romain GUILHAUMOU
• Phone: 491.38.96.56/75.65
• Email: Romain.GUILHAUMOU[@]ap-hm.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research targets four anti-infectives commonly prescribed in intensive care: ceftazidime, cefepime, cefotaxime and meropenem, used for severe infections For patient hospitalized in intensive care unit , there is little or no pharmacokinetic data for these four molecules.

Description:

Antibiotics, and especially beta-lactams, are among the most used drugs in the world. The good use of antibiotics and the prevention of selection of resistant strains has been a public health priority for many years. In this context, it is essential to obtain effective antibiotic concentrations at the site of infection. In order to obtain effective concentrations, ceftazidime, cefepime, cefotaxime, piperacillin and meropenem are administered in this population by continuous infusion at high dose. Although beta-lactams are mostly well tolerated, they can cause adverse effects such as severe neurological toxicities.

The critically ill patient has physiological alterations that can significantly alter the pharmacokinetics of drugs. Several studies have clearly shown that the pharmacokinetics of beta-lactams in the critically ill patient is different from those of other patients. Depending on the clinical context and the co-morbidities of the patient, sub-therapeutic or potentially toxic concentrations can be observed for the same dosage. The risk of ineffective treatment and the development of resistance remains, despite the high doses administered. In addition, this pharmacokinetic variability may be responsible for the observation of toxic concentrations and the occurrence of adverse effects in this population.

Following these arguments, therapeutic drug monitoring (TDM) of beta-lactams accompanied by personalized dosage adjustment appears to be an essential tool to optimize the management of critically ill patients. Although strongly recommended, the TDM of beta-lactams in the critically ill patient accompanied by a dosage adjustment is not currently performed systematically in all patients.

The objective of this study is to evaluate the impact of the use of a systematic therapeutic drug monitoring of beta-lactams in the critically ill treated with cefotaxime, ceftazidime, cefepime, meropenem or piperacillin, in terms of efficacy and prevention of neurotoxicity.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 180
• Est. completion date: October 31, 2020
• Est. primary completion date: June 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patient (age> 18 years)

• Patient hospitalized in intensive care for a duration greater than 7 days, treated with cefotaxime, ceftazidime, cefepime, piperacillin or meropenem according to a standardized dosing regimen.

Exclusion Criteria:

• Age <18

• Pregnant woman

• Patient allergic to beta-lactams

• No written informed consent by the patient or his/her (legal) representative

Related Conditions & MeSH terms

• Bacterial Infections
• Infection
• Infection, Bacterial

Intervention

Other:
• Blood sample
The blood samples will be taken from the patient's bed and then sent to the clinical pharmacology laboratory of Prof. Blin (DRC, Bat F, Timone Hospital).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	dosage of betalactamins concentrations	Target concentrations are determined from the PK/PD target defined for betalactamins in the intensive care patient, ie a steady-state concentration 100% of the time at 4-5xMIC.	14 days
Secondary	efficacy of the treatment with the clinical response at the end of treatment	Evaluate the efficacy of the treatment with the clinical response at the end of treatment and/or J14 according to the criteria of "resolution / improvement / failure" according to De Waele et al. (Intensive Care Medicine 2014 Sep; 40 (9): 1340-51)	14 days