Dose Escalation Trial of Intrasite Vancomycin Pharmacokinetics

• Status: Terminated
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Treatments: Anti-Bacterial Agents; Vancomycin

Criteria

Inclusion Criteria:

1. Posterior instrumented spinal surgery patients 18 years of age and older with instrumented fusion of at least three vertebral levels

1. Revision, elderly, obese, and diabetic patients will not be excluded since these patients are known to be at higher risk of wound infection and represent an important fraction of the elective surgical patient population.

2. Patients requiring IV Vancomycin for infection prophylaxis (i.e. due to cephalosporin allergy) will be eligible for participation in the IV Vancomycin group.

Exclusion Criteria:

Intrasite Vancomycin Study Arm Exclusion Criteria

1. Children under 18 years old

2. Patients not receiving instrumentation or having less than three segment surgery

• therefore having small wound bed surface areas, close operative quarters, and lower infection risk.

3. Patients not receiving wound drains

• drains provide the conduit for seroma fluid collection

4. Patients with known or suspected current infection

5. Use of systemic or topical antibiotics within 72 hours prior to surgery

• other than standard pre-op dose of ancef

6. Use of drugs or medications known to significantly increase the risk of renal toxicity within the perioperative period.

7. Patients with known significant allergy to Vancomycin

• Redman Syndrome patients will not be excluded

8. Use of IV Vancomycin for perioperative infection prophylaxis (for example, in cases of penicillin/cephalosporin allergy) will exclude patients from participation in the intrasite Vancomycin groups of the study.

• IV Vancomycin Study Arm Exclusion Criteria

1. Children under 18 years old

2. Patients not receiving instrumentation or having less than three segment surgery - therefore having small wound bed surface areas, close operative quarters, and lower infection risk.

3. Patients not receiving wound drains

• drains provide the conduit for seroma fluid collection

4. Patients with known or suspected current infection

5. Use of systemic or topical antibiotics within 72 hours prior to surgery

• other than study related IV Vancomycin

6. Use of drugs or medications known to significantly increase the risk of renal toxicity within the perioperative period.

7. Patients with known significant allergy to Vancomycin

• Redman Syndrome patients will not be excluded

8. Use of intrasite Vancomycin for infection prophylaxis will exclude patients from participation in the IV Vancomycin study group.