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Intradialytic Drug Removal by Short-daily Hemodialysis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Indiana University ( Indiana University School of Medicine )
ClinicalTrials.gov Identifier:
NCT00596167
First received: January 7, 2008
Last updated: February 24, 2016
Last verified: February 2016
  Purpose

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.

Condition Intervention
End Stage Renal Disease
Infection
Drug: Intravenous antibiotics

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Intradialytic Drug Removal by Short-daily Hemodialysis

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • 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). ] [ Designated as safety issue: No ]

    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.)



Enrollment: 6
Study Start Date: September 2007
Study Completion Date: September 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00596167

Locations
United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Investigators
Principal Investigator: Brian S Decker, MD, PharmD Indiana University School of Medicine
  More Information

Publications:
Responsible Party: Indiana University School of Medicine
ClinicalTrials.gov Identifier: NCT00596167     History of Changes
Other Study ID Numbers: 0609-18 
Study First Received: January 7, 2008
Results First Received: April 3, 2013
Last Updated: February 24, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Indiana University:
Short-daily hemodialysis
pharmacokinetics
levofloxacin
gentamicin
vancomycin

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Anti-Bacterial Agents
Vancomycin
Gentamicins
Levofloxacin
Ofloxacin
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 09, 2016