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

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

6

Phase

  • 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

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
Intervention / Treatment
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

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

Indiana University School of Medicine

Investigators

  • 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

September 1, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

January 7, 2008

First Submitted That Met QC Criteria

January 15, 2008

First Posted (Estimate)

January 16, 2008

Study Record Updates

Last Update Posted (Estimate)

March 25, 2016

Last Update Submitted That Met QC Criteria

February 24, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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