Pharmacokinetics and Pharmacodynamics of Linezolid Continuous and Intermittent Administration

NCT ID: NCT05801484

Last Updated: 2023-04-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-01

Study Completion Date

2024-07-30

Brief Summary

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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

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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.

Conditions

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Side-effect of Antibiotic Efficacy Pharmacokinetics Critical Illness Intensive Care Unit ICU

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Linezolid continuous infusion

In the intervention arm, Linezolid is administered 600 mg as loading dose as an infusion lasting one hour (flow rate 300 ml/h), followed by continuous infusion of 1200 mg linezolid over 24 hours (flow rate 25 ml/h) which is immediately initiated. The continuous infusion is administered until the end of the treatment.

Group Type EXPERIMENTAL

Linezolid continuous infusion

Intervention Type OTHER

Continuous infusion of 1200 mg linezolid in 24h, after an initial dose of 600 mg linezolid administered as one hour infusion

Linezolid Intermittent administration

In the comparator arm, 600 mg dose of Linezolid is administered as one-hour infusion (flow rate 300 ml/h). Two doses at 12-h intervals are infused until the end of the treatment.

Group Type ACTIVE_COMPARATOR

Linezolid continuous infusion

Intervention Type OTHER

Continuous infusion of 1200 mg linezolid in 24h, after an initial dose of 600 mg linezolid administered as one hour infusion

Interventions

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Linezolid continuous infusion

Continuous infusion of 1200 mg linezolid in 24h, after an initial dose of 600 mg linezolid administered as one hour infusion

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Iuliu Hatieganu University of Medicine and Pharmacy

OTHER

Sponsor Role collaborator

Cluj Municipal Clinical Hospital

OTHER

Sponsor Role lead

Responsible Party

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Bodolea Constantin

Assoc Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Constantin Bodolea, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca

Ligia A Hui, PharmD

Role: PRINCIPAL_INVESTIGATOR

University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca

Adina Popa, Prof PharmD

Role: STUDY_CHAIR

University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca

Laurian Vlase, Prof, PharmD

Role: STUDY_CHAIR

University Of Medicine and Pharmacy Iuliu Hatieganu, Cluj Napoca

Locations

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University Clinical Municipal Hospital

Cluj-Napoca, Cluj, Romania

Site Status RECRUITING

Countries

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Romania

Central Contacts

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Constantin Bodolea, MD, PhD

Role: CONTACT

+40726133845

Ligia A Hui, PharmD

Role: CONTACT

+40740385801

Facility Contacts

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Ligia A Hui, PharmD

Role: primary

+40740385801

Constantin Bodolea, MD

Role: backup

+40726133845

References

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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.

Reference Type BACKGROUND
PMID: 35453188 (View on PubMed)

Other Identifiers

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3/2022

Identifier Type: -

Identifier Source: org_study_id

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