Tobramycin Administered at the Beginning of Dialysis (ESRD)

February 24, 2021 updated by: Jean-Philippe Lafrance, Maisonneuve-Rosemont Hospital

Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session

The purpose of the study is to evaluate whether the administration of a full tobramycin dose (5 mg/kg) during the first 30 minutes of a hemodialysis session provides favorable pharmacokinetic parameters in subjects with end-stage renal disease who are suspected or has been diagnosed with Gram-negative rod-type infection.

It is anticipated that the administration of a single 5 mg/kg dose of tobramycin during the first 30 minutes of a hemodialysis session will achieve an optimal ratio of maximum tobramycin concentration to minimal inhibitory concentration (Cmax/CMI) of 8 to 10 while limiting the accumulation (trough < 2 mg/L before the next hemodialysis session) in end-stage renal disease subjects requiring intermittent hemodialysis sessions.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

STUDY DESIGN:

Prospective, monocentric, non-randomized, uncontrolled pharmacokinetic study

End-stage renal disease subjects who have been involved in an intermittent hemodialysis program and who have suspected or diagnosed Gram-negative rod-type infection.

Pharmacokinetic parameters: Tobramycin concentration analyses done at the beginning of hemodialysis session (before tobramycin administration), 30 minutes after completion of the infusion (will allow us to calculate the peak), during hemodialysis session (additional), at the end of hemodialysis session, between hemodialysis sessions (optional) and just before the next hemodialysis session (will allow us to analyse the trough).

RECRUITMENT PROCESS:

A systematic daily screening for hemodialysis hospitalized subjects or subjects followed at the outpatient clinic who have a suspicion or diagnosis of Gram-negative rod type infection will be made by the research coordinators. Software routinely used in the clinic at Maisonneuve-Rosemont Hospital (Gesphar, NumeRx, Oacis and Medurge) will be used to ensure the identification of potential subjects. The pharmacists responsible for validation of prescriptions at the pharmacy department will collaborate with the research team to help identifying eligible candidates. An eligibility assessment tool will be used and subjects who meet the inclusion criteria and do not meet any exclusion criteria will be considered as eligible candidates. Thereafter, additional baseline information will be collected from the medical file (e.g. ethnicity) or by questioning the subject. A member of the research team will addressed the eligible subject, will explain the study and present the Information Form and Informed Consent (FIC), that will document informed consent of the subject.

DATA COLLECTION:

A minimum of four blood samples and a maximum of six blood samples will be collected. The sampling scheme is as follows: at the beginning of hemodialysis session (before tobramycin administration), 30 minutes after completion of the infusion, during hemodialysis session (additional), at the end of hemodialysis session, between hemodialysis sessions (optional) and just before the next hemodialysis session.

A member of the research team will provide the tubes to the nursing, will write sampling times and will ship the blood samples to the laboratory.

STUDY SAMPLE:

Since the objective is to obtain robust pharmacokinetic parameters, the calculation of the sample size aims at a sufficient number of participants to obtain a convergence of facilitated pharmacokinetic parameters, thus obtaining values of coefficients of variation of less than 40%, while maintaining a statistical power of 80%. The calculation uses the variability of the parameters obtained by Veinstein et al. In this study, the residual clearance (Clnhd) is the parameter with the greatest variability (average of 10.4 mL / min with a standard deviation of 6.4 mL / min). Thus, the variability used in calculating the sample size is that of the parameter with the greatest variability, the residual clearance. The sample studied by Veinstein et al. not having the same characteristics as the subjects of the study, the variability could be greater than the reference sample and a safety margin of 30% is added. A total of 12 subjects to be recruited is therefore planned. No correction is applied for losses at the follow-up or withdrawal of consent considering the short duration of the study.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

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

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H1T 2M4
        • Maisonneuve-Rosemont Hospital

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:

  • Subjects aged 18 and over;
  • Subjects with end-stage renal disease who are on an intermittent hemodialysis program (three times a week, 3-4 hours) at the Hôpital Maisonneuve-Rosemont hemodialysis unit for at least one month;
  • Subjects with suspicion or diagnosis of Gram-negative rod-type bacteria infection for which an antibiotic is prescribed;
  • Subjects able to consent to the study (consent form read and signed by the subject).

Exclusion Criteria:

  • Contraindication or possible medical hazard related to the administration of tobramycin or to any ingredient in the formulation (e.g. sulphites), such as severe allergies or aminoglycoside-reported previous intolerances;
  • Variable residual renal function (e.g. acute or transient renal failure requiring occasional hemodialysis sessions, post-renal transplantation);
  • Conditions sensitive to the side effects of tobramycin (e.g. history of myasthenia gravis, Parkinson's disease, vestibular or auditory disorder);
  • Subjects with impaired volume of distribution (ie, severe burns [> 20%], significant ascites, decompensation for acute heart failure requiring hospitalization, admission to the critical care unit, cystic fibrosis, morbid obesity [dry weight greater than 50% of ideal weight]);
  • Pregnant or breastfeeding women;
  • Unstable hemodynamic status (risk of not tolerating / completing a 3-4 hour dialysis session);
  • Recent treatment with an aminoglycoside (<1 month);
  • Participation in another research protocol;
  • Inability to give free and informed consent.

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: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tobramycin
Subjects with end-stage renal disease who have been involved in an intermittent hemodialysis program and who have suspected or diagnosed Gram-negative rod-type infection
Drug: Tobramycin
5 milligrams per kilogram intravenous for one dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ratio of maximum tobramycin concentration to minimal inhibitory concentration
Time Frame: The timeframe for data collection for this outcome is 48 hours to 72 hours
In subjects receiving a single 5 mg/kg tobramycin dose during the first 30 minutes of a hemodialysis session, to determine the proportion of subjects in whom the maximum concentration is greater than or equal to 8 times that of the minimal inhibitory concentration
The timeframe for data collection for this outcome is 48 hours to 72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tobramycin trough level
Time Frame: The timeframe for data collection for this outcome is 48 hours to 72 hours
In subjects receiving a single 5 mg/kg tobramycin dose during the first 30 minutes of a hemodialysis session, to determine the proportion of subjects whose trough concentration of tobramycin is less than or equal to 2 mg / L.
The timeframe for data collection for this outcome is 48 hours to 72 hours
Residual clearance
Time Frame: The timeframe for data collection for this outcome is 48 hours to 72 hours
The timeframe for data collection for this outcome is 48 hours to 72 hours
Clearance associated with hemodialysis
Time Frame: The timeframe for data collection for this outcome is 48 hours to 72 hours
The timeframe for data collection for this outcome is 48 hours to 72 hours
Volume of distribution
Time Frame: The timeframe for data collection for this outcome is 48 hours to 72 hours
The timeframe for data collection for this outcome is 48 hours to 72 hours
Total area under the curve
Time Frame: The timeframe for data collection for this outcome is 0 to 48 or 72 hours (depending on time between the two dialysis)
The timeframe for data collection for this outcome is 0 to 48 or 72 hours (depending on time between the two dialysis)
Area under the curve between 0 to 24h after administration
Time Frame: The timeframe for data collection for this outcome is 0 to 24 hours
The timeframe for data collection for this outcome is 0 to 24 hours
Tobramycin concentration
Time Frame: The timeframe for data collection for this outcome is 24 hours to 72 hours
Tobramycin concentration 24h, 48h and 72h after administration
The timeframe for data collection for this outcome is 24 hours to 72 hours

Collaborators and Investigators

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

Sponsor

Maisonneuve-Rosemont Hospital

Investigators

  • Principal Investigator: Jean-Philippe Lafrance, MD, Maisonneuve-Rosemont Hospital

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 (Actual)

January 31, 2019

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

February 8, 2019

First Submitted That Met QC Criteria

April 3, 2019

First Posted (Actual)

April 5, 2019

Study Record Updates

Last Update Posted (Actual)

February 26, 2021

Last Update Submitted That Met QC Criteria

February 24, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-1619

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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