Intrawound Vancomycin Prophylaxis for Neural Stimulator (IV-DIRT)

Intrawound Vancomycin Prophylaxis During Stimulator Re-Implantation: A Multi-Center Randomized Controlled Trial

The implantable pulse generator (IPG) is a device that generates electrical current to stimulate the spine, heart, or brain for various chronic conditions. In neurosurgery, the IPG is implanted in a subcutaneous pocket under the collarbone. This pocket is highly avascular and thus, antibiotics administered intravenously cannot reach a potential surgical site infection (SSI). SSIs cause millions of health care dollars to be wasted due to repeat surgery and hospital re-admissions. The investigators hope to to determine the effects of "intrawound vancomycin-saline and IV antibiotics" compared to "saline and IV antibiotics" on the incidence of IPG SSI rates 6-months post-surgery.

Study Overview

• Status: Unknown
• Conditions: Surgical Site Infection; Deep Brain Stimulation; Vancomycin; Implantable Neural Stimulator
• Intervention / Treatment: Drug: Vancomycin Hydrochloride; Drug: Saline Solution

Detailed Description

Patients requiring neurosurgical IPG replacements will be recruited into this trial on a volunteer basis. The participants meeting the inclusion criteria will be randomized to either the treatment arm (intrawound Vancomycin-saline + IV antibiotics) or control arm (intrawound saline + IV antibiotics alone) by site in a 1:1 ratio. A sample size calculation using STplan determined that 405 patients per arm is required to reduce overall infection rate from 3.5% to 0.5% (80% power, α=0.05, two-tailed). Final sample size per arm will be 410 after generously accounting for loss to follow-up, non-compliance, and unrelated death.

The primary outcome will be a binary Yes/No on if IPG explantation due to infection was required within 6-months post-surgery.

This is a superiority trial and the investigators hypothesize intrawound Vancomycin-saline + IV antibiotics is superior to intrawound saline + IV antibiotics alone. An intention-to-treat analysis will be applied in a blinded manner once all patients have completed the trial and the database is locked.

The results of this trial will not only be applicable to neurosurgery, but also spine and cardiology.

• Study Type: Interventional
• Enrollment (Anticipated): 900
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Christopher R Honey, MD, DPhil; Phone Number: 6048755894; Email: chris.honey@telus.net
• Study Contact Backup: Name: Leah Polyhronopoulos, BSc; Email: leahpoly@mail.ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Recruiting
      • Vancouver General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• individuals who require INS replacement from Dr. C.R. Honey
• individuals who are between the ages of 18 to 80.
• individuals who consent to report any redness or swelling to their primary caregiver and follow-up as requested by their surgeon
• individuals who consent to keeping the study team informed of any medical concerns they may have regarding their INS for a minimum of 6 months postoperatively
• individuals who are capable of providing informed consent

Exclusion Criteria:

• individuals who have a history of autoimmune disease
• individuals who are undergoing any surgery or procedural intervention within six-months post-operatively of entrance into this study
• individuals who are on immunosuppression or any medication that would influence infection susceptibility
• individuals who are allergic to Vancomycin or Cefazolin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin; These patients will receive intrawound Vancomycin-saline and IV antibiotics	Drug: Vancomycin Hydrochloride; Individuals in the experimental arm will receive intrawound Vancomycin-saline + IV antibiotics; Drug: Saline Solution; Individuals in the control arm will receive intrawound saline solution
Placebo Comparator: Saline; These patients will receive intrawound saline + IV antibiotics alone	Drug: Saline Solution; Individuals in the control arm will receive intrawound saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device explantation 6 months post surgery	The primary outcome measure will be determined at the 6 month post surgery point, where the binary yes/no question, "was the INS device explanted", will be answered.	6 months

Collaborators and Investigators

• Sponsor: University of British Columbia

Publications and helpful links

General Publications

• Ghobrial GM, Cadotte DW, Williams K Jr, Fehlings MG, Harrop JS. Complications from the use of intrawound vancomycin in lumbar spinal surgery: a systematic review. Neurosurg Focus. 2015 Oct;39(4):E11. doi: 10.3171/2015.7.FOCUS15258.
• Doshi PK. Long-term surgical and hardware-related complications of deep brain stimulation. Stereotact Funct Neurosurg. 2011;89(2):89-95. doi: 10.1159/000323372. Epub 2011 Feb 2.
• Caroom C, Tullar JM, Benton EG Jr, Jones JR, Chaput CD. Intrawound vancomycin powder reduces surgical site infections in posterior cervical fusion. Spine (Phila Pa 1976). 2013 Jun 15;38(14):1183-7. doi: 10.1097/BRS.0b013e31828fcfb5.
• Martin JR, Adogwa O, Brown CR, Kuchibhatla M, Bagley CA, Lad SP, Gottfried ON. Experience with intrawound vancomycin powder for posterior cervical fusion surgery. J Neurosurg Spine. 2015 Jan;22(1):26-33. doi: 10.3171/2014.9.SPINE13826.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2017
• Primary Completion (Anticipated): September 15, 2021
• Study Completion (Anticipated): December 15, 2021

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 18, 2017

Study Record Updates

• Last Update Posted (Actual): October 30, 2020
• Last Update Submitted That Met QC Criteria: October 29, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Vancomycin; Surgical Site Infection; Deep Brain Stimulation; Implantable Neural Stimulator
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Wound Infection; Surgical Wound Infection; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: H16-01496

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes