Pharmacokinetics of an Aminoglycoside in Hemodialysis Patients. (DIAMS)

July 15, 2020 updated by: University Hospital, Limoges

Aminoglycosides are widely used for the treatment of Gram-negative bacilli and Staphylococcus aureus infections because of their effectiveness and low cost. Nevertheless, many aspects of their optimal use in hemodialysis patients remain unsolved and little is known about their pharmacokinetics in this context. The current practice for prescribing aminoglycosides to these particular patients consists in giving after each hemodialysis session about half the dose usually given to patients with normal renal function.

However, theoretical considerations and emerging clinical data suggest that this may not be the most beneficial dosing regimen as efficient peak concentrations are often not attained and the occurrence of ototoxicity and nephrotoxicity is still frequent.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Recent evidence about the pharmacokinetics and pharmacodynamics of aminoglycosides strongly supports administration of aminoglycosides before, rather than after, hemodialysis. Therapeutic drug monitoring using pharmacokinetic modeling is currently used in non-hemodialysis patients. However, the PK tools employed are not suitable to dialysis patients.

For aminoglycosides, the ratio of peak to Minimal Inhibitory Concentration (MIC) has been shown to be the parameter that best correlates with clinical efficacy, whilst prolonged exposure to high concentrations have been related to either nephrotoxicity or ototoxicity. Additionally, aminoglycosides are mostly excreted as unchanged drugs in urine and their clearance is directly proportional to the glomerular filtration rate. The elimination half-life of aminoglycosides is approximately 1.5-3 hours in adults with normal renal function, but is greatly prolonged up to 36-70 hours in patients with end-stage renal failure. In a standard patient, aminoglycosides are administered as a single dose, over a short time interval, to obtain an elevated blood peak concentration (the effective level). The next injection is not administered before 24 hours, to allow the patient to wash out the aminoside and to minimize the residual blood concentration (the toxic level). The aim here is to maximize the peak concentration during a fair amount of time (by repeating the peaks) and to minimize the overall drug exposure, responsible for the toxicity.

For the renal impaired patient, our hypothesis is that the hemodialyzer can be regarded as a kidney. Thus, the administration of the aminoside at the beginning of the hemodialysis could lead to profiles of elimination comparable to those observed in normorenal patients.

The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Limoges, France, 87042
        • CHU LIMOGES - Laboratoire de Pharmacologie
      • Limoges, France, 87042
        • CHU LIMOGES - Service Néphrologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age upper to 18 years
  • Patients hospitalized in the "Service de Néphrologie - Hémodialyse, Transplantations, CHU de Limoges"
  • Patients requiring chronic hemodialysis
  • Patients requiring a treatment by aminoglycosides
  • Patients willing to give their written informed consent for their participation to the study
  • Patients affiliated to the French social security system or equivalent

Exclusion Criteria:

  • Patients under legal protection
  • Patients unable or unwilling to provide informed consent and not under legal protection
  • Patients deprived of liberty
  • Contraindications to gentamicin
  • Pregnant or breast-feeding women or women of childbearing potential without efficient contraception (based on declaration)
  • Patients with any altered mental status or any psychiatric condition that would interfere with the understanding of the study
  • Patients enrolled in another clinical trial testing drugs or therapeutic strategies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: hemodialysis patients
The administration of gentamicin at the beginning of the hemodialysis.
Drug: Gentamicin

The decision to introduce the antibiotic is made during a session or between two sessions according to both the clinicians usual procedure.

Depending on the number of injections, 8 to 10 blood samples will be drawn per patient. Clinical and biological data will be concomitantly collected (e.g., hemodialysis session duration, creatinine clearance…).

The number of blood sampling and the time schedule will be adapted to the prescription and the possible follow-up of the treatment after the first injection. Whatever the time is between the first injection and the following dialysis session, a sampling will be performed 30 minutes after the end of the injection (T1), 8h after the end of the injection (T2), juste before (TAD), in the middle (TMD) and at the end of the dialysis (TFD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concentration curves of gentamicin
Time Frame: 1 week

The research aims at performing a population pharmacokinetic (POPPK) study of gentamicin when given to hemodialysis patients.

The ability to describe the concentration curves versus time (Biais (%) between the observed concentrations and the concentrations predicted by the model).
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Limoges

Investigators

  • Principal Investigator: Pierre MARQUET, MD, CHU Limoges

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2013

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

January 1, 2016

Study Registration Dates

First Submitted

October 31, 2013

First Submitted That Met QC Criteria

November 6, 2013

First Posted (Estimate)

November 13, 2013

Study Record Updates

Last Update Posted (Actual)

July 17, 2020

Last Update Submitted That Met QC Criteria

July 15, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I12008 DIAMS

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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