Safety and Efficacy of Strategy to Prevent Drug-Induced Nephrotoxicity in High-Risk Patients

Overview

For more than fifty years, vancomycin has been cited as a nephrotoxic agent. Reports of vancomycin induced kidney injury (a.k.a vancomycin induced nephrotoxicity or VIN), have waxed and waned throughout the years for various reasons. Recently, VIN has reemerged as a clinical concern. This may be due to various reasons, including new dosing recommendations as well as an increased prevalence of risk factors associated with vancomycin induced nephrotoxicity. This study aims to evaluate a strategy which attempts to reduce kidney damage from vancomycin use.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: September 2013

Interventions

  • Drug: Vancomycin
    • Dose optimized vancomycin. Target trough: 15 – 20 mg/L for Health Care Associated Pneumonia, Osteomyelitis, Septic Arthritis, Endocarditis and Bacteremia; Target trough: 10 – 20 mg/L for Acute Bacterial Skin and Skin Structure Infections;
  • Drug: Ceftaroline
    • Dose based on package insert labeling CrCL > 50 mL/min: 600 mg IV q12h CrCL 31-50 mL/min: 400 mg q12h CrCL 15-30 mL/min: 300 mg q12h CrCL < 15mL/min: 200 mg q12h;
  • Drug: Daptomycin
    • Dose based on renal function and literature dosing recommendations CrCL ≥ 30 mL/min: 6 – 10 mg/kg IV q24h CrCL < 30 mL/min: 6 – 10 mg/kg IV q48h
  • Drug: Linezolid
    • 600 mg IV/PO q12h

Arms, Groups and Cohorts

  • Active Comparator: Vancomycin
  • Active Comparator: Comparator

Clinical Trial Outcome Measures

Primary Measures

  • Nephrotoxicity
    • Time Frame: Day 1 and daily serum creatinine assessment up to date of discharge
    • Increase in SCr of 0.5 mg/dL or 50% above baseline for at least two consecutive days. This measure will be reported as proportion of patients with nephrotoxicity within each group in relation to the number of patients in each group.

Secondary Measures

  • Acute Kidney Injury Network Modified Definition of Nephrotoxicity
    • Time Frame: Day 1 and daily serum creatinine assessment up to date of discharge
    • An abrupt (within 48 hour) reduction in kidney function with one or more of the following 1) Increase in SCr ≥ 0.3 mg/dL 2) Increase SCr ≥ 50% or 3) Decreased urine output (< 0.5 ml/kg/hr x 6 hrs). This measure will be reported as proportion of patients with acute kidney injury within each group in relation to the number of patients in each group.
  • Clinical Success
    • Time Frame: Daily assessment of signs and symptoms of infection
    • Clinical success is a composite endpoint of those patients with clinical cure or improvement in clinical signs and symptoms of infection (i.e. SIRS criteria, and microbiology). This measure will be reported as the proportion of patients with clinical success in each group compared to the the total number of patients in the group.

Participating in This Clinical Trial

Inclusion Criteria

  • Aged 18 years or older
  • Receiving intravenous vancomycin for the treatment of healthcare associated pneumonia, osteomyelitis/septic arthritis, endocarditis/bacteremia, or acute bacterial skin and skin structure infections
  • Expected to receive vancomycin for at least 72 hours and are within the first 72 hours of therapy
  • Have at least two or more of the following risk factors for drug-induced nephrotoxicity: a) receipt high-dose vancomycin therapy (greater than or equal to four grams per day) b) receipt of vasopressors c) receipt of nephrotoxic drugs (i.e. aminoglycosides, furosemide, acyclovir, amphotericin b, colistin, and intravenous contrast dye) d) pre-existing renal dysfunction (i.e. SCr greater than or equal to 1.5 mg/dL).

Exclusion Criteria

  • Pregnancy
  • End-stage renal disease
  • Receipt of more than 4 grams of vancomycin prior to enrollment on current admission
  • Absolute neutrophil count < 1000/mm3

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Henry Ford Health System
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jose Vazquez, M.D. – Henry Ford Health System
  • Overall Official(s)
    • Jose Vazquez, M.D., Principal Investigator, Henry Ford Hospital

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