Optimizing Linezolid Dosing in Patients With Advanced Renal Impairment: a Therapeutic Drug Monitoring-based Evaluation

NCT ID: NCT07138521

Last Updated: 2025-08-24

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

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-15

Study Completion Date

2026-05-15

Brief Summary

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The goal of this clinical trial is to adjust the Linezolid dose according to its blood level in adults with kidney diseases. It will also learn about the safety of linezolid. The main questions it aims to answer are:

* How often does linezolid require level monitoring?
* How often does linezolid require dose adjustment?
* What medical benefits do participants have when linezolid level monitoring is applied? Researchers will compare two dose reduction regimens when they have evidence of overexposure to determine which regimen is more effective in preventing thrombocytopenia (Platelet drop).

Participants will:

* Withdrew linezolid level every 2 to 4 days of the antibiotic course.
* Visit the clinic twice for checkups and tests.

Detailed Description

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Linezolid is a crucial antibiotic prescribed for the treatment of various infectious diseases such as pneumonia, skin infections, and catheter-related bloodstream infections. Linezolid covers gram-positive bacteria, including Methicillin-resistant Staphylococcus Auris (MRSA) and Vancomycin-resistant Staphylococcus Auris (VRSA).

Recently, Linezolid usage has become favorable for chronic kidney disease (CKD) patients to preserve the remaining residual renal function by avoiding nephrotoxic antibiotics such as vancomycin and aminoglycosides. However, linezolid-induced thrombocytopenia hinders linezolid use in the CKD population due to accumulation and overexposure. Recent literature suggested implementing a therapeutic drug monitoring (TDM) approach to modify the dose regimen and minimize linezolid toxicity.

The obstacle faced was the lack of clear TDM-based linezolid modification guidelines for CKD patients. To overcome this issue, we conducted a pilot study involving 15 patients (7 ESRD, 5 CKD, and 3 AKI on top of CKD). Patients with evidence of toxic levels (8 patients) underwent dose adjustment from 600mg every 12 hours to 300mg every 12 hours.

Dose reduction by 50% with no change in dose interval resulted in a decrease in supratherapeutic trough levels. However, these levels, while lower, did not consistently reach the predefined target therapeutic range (2-8 mg/dl).

The recent approach we are investigating now is to both lower the dose and elongate the interval.

The aim of the work is to optimize renal dosing adjustment with patients having linezolid by investigating whether once-daily dosing administration of linezolid provides better trough-range targeting over twice-daily targeting.

Research Steps

1. Patients were interviewed and selected according to the study's selection criteria.
2. Blood tests were taken before the start of the study to assess their condition and record their medical history before starting linezolid treatment.
3. Participants were divided into three groups based on linezolid drug concentrations compared to the pre-defined target therapeutic range, as determined by the pharmacotherapy monitoring guidelines:

I. Group 1: Within the therapeutic range: No intervention and continued linezolid 600 mg every 12 hours.

II. Group 2: Above the therapeutic range and within the toxicity range: Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 300 mg every 12 hours.

III. Group 3: Above the therapeutic range and within the toxicity range: Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 600 mg every 24 hours.
4. Patient follow-up was conducted at the end of the study and comparisons were made between the different groups.

Conditions

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Kidney Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group 1

Linezolid level within therapeutic range

Group Type EXPERIMENTAL

Linezolid (IV and PO)

Intervention Type DRUG

No dose change and continued linezolid 600 mg every 12 hours.

Group 2

Above the therapeutic range and within the toxicity range

Group Type EXPERIMENTAL

Linezolid (IV and PO)

Intervention Type DRUG

Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 300 mg every 12 hours.

Group 3

Above the therapeutic range and within the toxicity range

Group Type EXPERIMENTAL

Linezolid (IV and PO)

Intervention Type DRUG

Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 600 mg every 24 hours.

Interventions

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Linezolid (IV and PO)

No dose change and continued linezolid 600 mg every 12 hours.

Intervention Type DRUG

Linezolid (IV and PO)

Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 300 mg every 12 hours.

Intervention Type DRUG

Linezolid (IV and PO)

Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 600 mg every 24 hours.

Intervention Type DRUG

Other Intervention Names

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600-twice 300-twice 600-once

Eligibility Criteria

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Inclusion Criteria

* Advanced renal impairment, Hemodialysis patients

Exclusion Criteria

* Pregnancy, Lactating females, Advanced Liver impairment, Cases using antidepressants or antipsychotics, Cases suffering from Hematological blood diseases, and/or chronic Immune thrombocytopenia.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexandria University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Central Contacts

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Hanaa Said, PharmD, Alexandria University

Role: CONTACT

+201062416139

Related Links

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https://pubmed.ncbi.nlm.nih.gov/37301313

Dose optimisation of linezolid in critically ill patients based on a population pharmacokinetic model: A two-centre prospective interventional study

https://pubmed.ncbi.nlm.nih.gov/34040351

Pharmacokinetics of Linezolid Dose Adjustment for Creatinine Clearance in Critically Ill Patients: A Multicenter, Prospective, Open-Label, Observational Study

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035989

Dosage Strategy of Linezolid According to the Trough Concentration Target and Renal Function in Chinese Critically Ill Patients

https://pubmed.ncbi.nlm.nih.gov/31109977

Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety

https://pubmed.ncbi.nlm.nih.gov/25108880

Analysis of thrombocytopenic effects and population pharmacokinetics of linezolid: a dosage strategy according to the trough concentration target and renal function in adult patients

Other Identifiers

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Linezolid TDM

Identifier Type: -

Identifier Source: org_study_id

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