Dose Escalation Trial of Intrasite Vancomycin Pharmacokinetics
Status:
Terminated
Trial end date:
2013-12-01
Target enrollment:
Participant gender:
Summary
Surgical wound infections remain a serious problem despite aseptic techniques and the use of
prophylactic systemic antibiotics. Such infections can occur at rates up to ~20% in high-risk
patients receiving long segment instrumented spinal fusions for deformity correction and
present potentially catastrophic consequences. Given this, the high cost of treatment, and a
payer system unable to support such expenses, investigators must make every effort to find
new cost-effective ways to prevent these complications.
Increasingly surgeons have sought to address this problem by placing lyophilized Vancomycin
into spinal surgery wounds immediately prior to wound closure. This method, known as
"intrasite" application, is adapted from techniques used to prevent infection in joint
replacement surgeries. The motivation for this practice is to maximize antibiotic
concentration within the wound while minimizing systemic concentration and toxicity, (the
inverse of the situation when using IV antibiotics). While the popularity of intrasite
delivery has grown rapidly, this has occurred without prospective scientific evidence.
Recently, three retrospective papers including nearly 2,500 treated patients, indicated that
intrasite Vancomycin reduces wound infections without increasing adverse events[1-3].
However, there are no published data on the dosing or pharmacokinetics of intrasite
Vancomycin, let alone prospective trials of its efficacy and safety.
The investigators propose to perform the first prospective trial of intrasite Vancomycin
pharmacokinetics and safety. Study objectives will include standardizing application and
dosing, defining peak/trough concentrations and clearance parameters, verifying bactericidal
potency, and dose selection for use in future studies. This will be accomplished by enrolling
groups of patients (n=10) to receive one of three doses of intrasite lyophilized Vancomycin
(3, 6 or 12 mg/cm2), prior to wound closure. Vancomycin concentrations in venous blood and
wound seroma fluid will be measured at regular intervals after surgery to establish
pharmacokinetic parameters. Preliminary data regarding local and systemic adverse events
including wound healing, fusion rate, and toxicity will be prospectively collected. The
ultimate goal of this learning-phase study is to gather sufficient information regarding
application, dosing, pharmacokinetics, measurement strategies, and adverse events to prepare
for a Phase III efficacy trial.