Clinical trial NCT05801484: Pharmacokinetics and Pharmacodynamics of Linezolid Continuous and Intermittent Administration
Official title: Continuous Infusion Versus Intermittent Administration of Linezolid - Impact on Clinical Outcome and Adverse Reactions in Critically Ill Patients: a Pharmacokinetic and Pharmacodynamic Prospective Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Side-effect of Antibiotic
Efficacy
Pharmacokinetics
Critical Illness
Intensive Care Unit ICU
Keywords: continuous infusion
intensive care unit
critically ill
linezolid
pharmacokinetics
pharmacodynamics
Lead sponsor: Cluj Municipal Clinical Hospital
Sponsor class: OTHER
Collaborators: name: Iuliu Hatieganu University of Medicine and Pharmacy
First posted: 2023-04-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: open, prospective, randomized design, with two groups of patients (group with intermittent administration and group with continuous administration of the same daily dose of linezolid).
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the therapeutic efficacy expressed in pharmacokinetic/pharmacodynamic (PK/PD) indices, the clinical response and the risk of adverse reactions following the continuous and intermittent administration of linezolid in critical patients in the Intensive Care Unit.

Subject inclusion criteria:

A minimum of 30 subjects in each group will be included in the study, in accordance with the study inclusion criteria:

* patients hospitalized in the intensive care unit,
* female or male sex,
* age over 18 years,
* linezolid is prescribed by the attending physician, in empirical or targeted treatment

Exclusion criteria:

Patients who have documented severe liver failure (Child-Pugh C score). Patients who refuse to sign the informed consent

Detailed description: The clinical study will be conducted in accordance with the protocol approved by the Ethics Commission of the "I.Haţieganu" University of Medicine and Pharmacy and the Ethics Commission of the Municipal Clinical Hospital, from Cluj-Napoca, in accordance with the rules of good clinical study practice.

The study will take place on the Intensive Care Unit of University Clinical Municipal Hospital from Cluj-Napoca, Romania. The analysis of blood drug concentration will be carried out at University of Medicine and Pharmacy 'Iuliu Hatieganu', Pharmacokinetics and Biopharmacy Laboratory, from Cluj-Napoca, Romania.

The objectives of the study are:

* Determination and the comparison of the pharmacokinetic and pharmacodynamic parameters of linezolid administration following intermittent infusion or continuous infusion, in critically ill patients.
* Determination of the minimum inhibitory concentrations (MIC) for linezolid for the identified bacteria (Staphylococcus aureus, Coagulase-Negative Staphylococcus, Enterococcus spp., Streptococcus pneumoniae).

The study will be conducted in the ICU Department of the Municipal Clinical Hospital in Cluj-Napoca, Romania, following an open, prospective, randomized design, with two groups of patients (group with intermittent infusion and group with continuous infusion of the same daily dose of linezolid). The patients that will be included in each group will be the patients in need of intensive care who are prescribed linezolid by the attending physician, as empirical or targeted therapy.

Given the low light stability of the linezolid solution, the infusion bag will be protected with an opaque cover provided by the manufacturer throughout the infusion period. The administration will be carried out with the help of an infusomate.

The duration of the therapy will be established, for each patient, by the attending physician depending on the type, location and severity of the infection in accordance with the recommendations of the therapeutic guidelines.

Throughout the duration of the study, the subjects will receive the treatment according to the recommendations of the attending physician, regardless of the group they belong to, the only difference between the groups refers to the type of infusion used to administer linezolid.

Blood samples (10 samples) will be taken from each volunteer, according to the following schedule: immediately before the start of the infusion (T0) and at 1, 2, 4, 8, 12, 18, 24, 36, 48 hours from initiation of drug infusion. Then, a single daily sample will be taken until the end of the treatment. Blood samples will be used to determine plasma concentrations of linezolid.

The efficacy and safety of the treatment will be evaluated using clinical and paraclinical data which will be correlated with the pharmacokinetic parameters determined for each type of treatment (continuous infusion or intermittent infusion). The data will be recorded in a case report form without disclosing the identity of the patients (each patient will receive a code at the beginning of the study).

Each subject will be followed until discharge or a maximum of 30 days after initiation of therapy.

Eligibility criteria: Inclusion Criteria:

* patients hospitalized in the intensive care unit,
* female or male sex,
* age over 18 years,
* linezolid is prescribed by the attending physician, in empirical treatment or based on the antibiogram.

Exclusion Criteria:

* documented severe liver failure (Child-Pugh C).
* no informed consent signed

Primary outcomes:
measure: Linezolid plasmatic concentrations
timeFrame: first 2-14 days (during treatment)
Secondary outcomes:
measure: Linezolid clinical efficacy
timeFrame: from day 1 to day 30 after therapy initiation
measure: Linezolid adverse reactions
timeFrame: from day 1 to day 30 after therapy initiation
Other outcomes:
measure: Linezolid drug-drug interactions
timeFrame: from day 1 to day 30 after therapy initiation
measure: Determination of the minimum inhibitory concentration (MIC) for linezolid for the identified bacteria
timeFrame: from day 1
Locations:
city: Cluj-Napoca
country: Romania
facility: University Clinical Municipal Hospital
state: Cluj
Study officials:
affiliation: University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca
name: Constantin Bodolea, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca
name: Ligia A Hui, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca
name: Adina Popa, Prof PharmD
role: STUDY_CHAIR
affiliation: University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca
name: Laurian Vlase, Prof, PharmD
role: STUDY_CHAIR
References:
citation: Hui LA, Bodolea C, Vlase L, Hiriscau EI, Popa A. Linezolid Administration to Critically Ill Patients: Intermittent or Continuous Infusion? A Systematic Literature Search and Review. Antibiotics (Basel). 2022 Mar 24;11(4):436. doi: 10.3390/antibiotics11040436.