Intradialytic Drug Removal by Short-daily Hemodialysis

February 24, 2016 updated by: Indiana University School of Medicine

Short-daily hemodialysis is increasingly becoming a preferred alternative to the conventional intermittent (three times per week) hemodialysis schedule. Studies have shown that short-daily dialysis improves a patient's quality of life, high blood pressure, anemia and calcium-phosphorus balance. Infection, however, will likely remain a persistent problem for dialysis patients regardless of the frequency of treatments. There is currently a wealth of information to guide doctors on how much and how frequently to give an antibiotic for patients who receive intermittent (thrice weekly) hemodialysis. However, there is very little information on how to prescribe antibiotics for patient's receiving short-daily hemodialysis. This study will develop drug dose guidelines for patients receiving short-daily hemodialysis for three frequently used antibiotics, vancomycin, levofloxacin and gentamicin. These guidelines will assist doctors so that patients receive the most effective dose and frequency of an antibiotic to treat their infection.

The following is the study hypothesis which will be tested with two-sided, one sample t-tests comparing the AUC observed to historical measures8.

1) Vancomycin, levofloxacin and gentamicin are removed to a greater extent by short-daily hemodialysis than intermittent hemodialysis.

The following are the specific aims:

  1. Determine the interdialytic pharmacokinetics of vancomycin, gentamicin, and levofloxacin by short-daily HD.
  2. Determine the extent of vancomycin removal when administered during the last hour of short-daily HD.
  3. Develop drug-dosing guidelines for vancomycin, gentamicin and levofloxacin for patients receiving short-daily HD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Despite improvements in dialysis machine and filter technology and refinements in providing an adequate "dose" of HD, patients receiving thrice-weekly hemodialysis (HD) have an alarming 20% annual mortality rate. Concomitant with this high mortality rate, patients with end stage renal disease (ESRD) also endure poorer qualities of life and medical complications such as anemia, infection, accelerated cardiovascular disease and bone disease associated with calcium-phosphorus disequilibrium. Recently, quotidian dialysis regimens, which include both the short-daily and nocturnal modalities, have emerged as dialytic approaches that appear to improve the patient's quality of life and attenuate the medical complications associated with ESRD1- 4. Specifically, recent studies have documented improvements in a patient's quality of life as measured by both general instruments (SF-36) and by renal disease specific tools. Short-daily HD regimens have also led to improvements in anemia allowing reductions in doses of erythropoietin. Similarly, in one study blood pressure control was improved with short-daily HD to such an extent that the majority of the study patients were eventually off of all antihypertensive medications. Phosphorus control has also improved with hemeral and especially nocturnal short-daily regimens. In one study of patients receiving nocturnal HD, all of the patients were completely weaned of their phosphorus binders and actually required intradialytic phosphorus supplementation. Finally, nutritional status also appears to be enhanced in studies of short-daily HD with increases in both appetite and weight gain observed. The medical benefits observed in these studies are believed to be secondary to the enhanced solute clearance and better extra-cellular volume management that short-daily HD affords as compared to intermittent HD. In particular, the nocturnal regimen appears especially effective since it provides a higher "dose" of HD than its hemeral counterpart.

According to the most recent United States Renal Data Service (USRDS) compilation, infection continues to exact a heavy toll among dialysis patients. The most recent USRDS mortality rate attributable to sepsis for dialysis patients was 27.0%. Despite the reported improvements in quality of life and medical complications provided by short-daily HD, infection will likely remain a persistent medical issue for dialysis patients. As a result, the appropriate provision of antibiotic therapy to patients receiving hemodialysis will remain paramount. Currently, there are no studies that have evaluated the pharmacokinetics of the commonly used antibiotics in the growing short-daily HD population. With no specific guidelines, pharmaco-kinetic estimations and frequent drug levels have been utilized to direct antibiotic dosing. This is likely not the best therapeutic approach and may not be the most cost-effective. This study will attempt to address this deficit in the clinical knowledge for three commonly used antibiotics, vancomycin, levofloxacin and gentamicin. The drug dosing guidelines developed from this study will ensure that this patient population receives the optimum antibiotic therapy to treat their infection in the most cost-effective manner.

Utilizing drug level data from an as yet unpublished study on the removal of gentamicin by thrice weekly dialysis, we configured the pharmacokinetic modeling software ADAPT to compare the serum levels of gentamicin during intermittent and short-daily HD. For the short-daily HD simulation, the ADAPT software demonstrated two periods of increased removal of gentamicin corresponding to the two sessions of short-daily HD (Figure 1). The purpose of the present study is to demonstrate in vivo that this is indeed true for gentamicin, as well as for vancomycin and levofloxacin.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • > 18 years old
  • currently receiving short-daily HD six times per week
  • have no other acute intercurrent illness

Exclusion Criteria:

  • history of a vancomycin, gentamicin or levofloxacin allergy
  • weight within ± 30% of their ideal body weight
  • Hgb < 10 mg/dl

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

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Intravenous antibiotics
Intervention: administer intravenous vancomycin, gentamicin and levofloxacin. This study will determine the pharmacokinetics of intravenous vancomycin, gentamicin and levofloxacin in subjects receiving short-daily hemodialysis. There will not be a control arm for this study. The intervention for this arm will be to administer intravenous vancomycin, gentamicin and levofloxacin and draw blood samples at periodic intervals. The blood samples will be tested for these medications and pharmacokinetic analysis will be performed.
Drug: Intravenous antibiotics
Each subject will receive a single dose of 15 mg/kg vancomycin; 2 mg/kg gentamicin and 250 mg levofloxacin administered intravenously over a one-hour infusion period through the venous limb of their HD access (or tunneled catheter) via an IV pump.
Other Names:
  • Vancocin (vancomycin)
  • Levaquin (levofloxacin)
  • Gentamicin (gentamicin)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Intradialytic Clearance of Levofloxacin, Gentamicin and Vancomycin in Patients Receiving Short-daily Hemodialysis
Time Frame: Serum concentrations for each drug will be determined from blood samples at 0 (pre-infusion), 30, 60 minutes (end of infusion).

The intradialytic clearance of levofloxacin, gentamicin and vancomycin will be determined in patients receiving short-daily hemodialysis.

(Of important note, due to technical issues the levofloxacin data was not able to be used for the analysis. Only the gentamicin and vancomycin data was analyzed.)
Serum concentrations for each drug will be determined from blood samples at 0 (pre-infusion), 30, 60 minutes (end of infusion).

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indiana University School of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Brian S Decker, MD, PharmD, Indiana University School of Medicine

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 15, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 24, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0609-18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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