Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO) (VANCO)

Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (Vancomycin Study)

The Vancomycin Study is a multi-center, prospective randomized controlled trial that will compare the proportion of deep surgical site infections within 6 months in patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder at the time of fracture fixation.

Study Overview

• Status: Completed
• Conditions: Post Operative Surgical Site Infection
• Intervention / Treatment: Drug: Vancomycin antibiotic powder

Detailed Description

Primary Aim: Compare the proportion of deep surgical site infections within 6 months in patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder.

Primary Hypothesis: The proportion of deep surgical site infections will be lower for patients treated with local Vancomycin powder.

Secondary Aim #1: Compare antibiotic sensitivities of the bacteria in the patients who develop deep surgical site infections in study patients treated with local Vancomycin powder compared to those treated without local Vancomycin powder.

Hypothesis 1: In the patients who develop infections, the antibiotic sensitivity profiles between patients treated with local Vancomycin powder will be non-inferior to those treated without local Vancomycin powder.

Secondary Aim #2: Build and validate a risk prediction model for the development of deep surgical site infections in patients treated without local Vancomycin powder. (b) Explore whether the effect of local Vancomycin powder is modified by the predicted risk of infection.

Hypothesis 2: Patient (e.g. medical co-morbidities) and injury (e.g open fractures) factors will be highly predictive of infection risk.

Hypothesis 3: Patients with higher predictive risk will experience greater benefit from local antibiotics.

• Study Type: Interventional
• Enrollment (Actual): 1036
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland R Adams Cowley Shock Trauma Center

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:

• All "high energy" tibial plateau fractures treated operatively with plate and screw fixation.

• We define "high energy" tibial plateau fractures as patients who are either:

  • Initially treated with an external fixation (with or without limited internal fixation) and treated definitively more than 3 days later after swelling has resolved.
  • Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
  • Any tibial plateau fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds.

• All "high energy" pilon (distal tibial plafond) fractures treated operatively with plate and screw fixation. We define "high energy" pilon fractures as patients who are either:

  • Initially treated with an external fixation (with or without fibula fixation or limited internal fixation) and treated definitively more than 3 days later after swelling has resolved.
  • Any open type I, II, or IIIA fracture, regardless of timing of definitive treatment.
  • Any tibial pilon fracture associated with ipsilateral leg compartment syndrome fasciotomy wounds.
• Ages 18 to 80 years
• Patients may have co-existing non-tibial infection, with or without antibiotic treatment.
• Patients may have risk factors for infection including diabetes, immunosuppression from steroids or other medications, HIV, or other infections.
• Patients may have a head injury
• Patients may have a portion of the fixation (e.g. fibula fixation in pilon or percutaneous screws across a tibial plateau fracture) prior to definitive plate fixation, at the initial surgery before randomization.
• Patients may have other orthopedic and non-orthopaedic injuries.
• Patients may have pre-existing musculoskeletal injuries, be non ambulators, or have spinal cord injuries.
• Women and minorities are included

Exclusion Criteria:

• The study injury: tibial plateau, pilon, is already infected at time of study enrollment.
• Patient speaks neither English nor Spanish.
• Patients who have already had definitive fixation prior to enrollment in the study.
• Severe problems with maintaining follow-up (e.g. patients who are homeless at the time of injury or those how are intellectually challenged without adequate family support).
• Patients with allergies, drug administration reactions, or other sensitivities to Vancomycin (such as a history of Redman's Syndrome).
• Pregnancy.
• The study injury is a type IIIB or IIIC open fracture.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vancomycin Antibotic Powder; Participants in the treatment group will receive the study intervention of a maximum dose of 1000mg of Vancomycin antibiotic powder in their wound bed, which is placed right before wound closure. Vancomycin antibiotic powder may be combined with normal saline as per clinical practice at the participating institution. In addition, participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection.	Drug: Vancomycin antibiotic powder; At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.
No Intervention: Standard of Care; Participants in this group will receive standard of care treatment for their injury, to include all institution specific standard treatment (prophylactic and otherwise) for preventing and treating infection. Participants in this group will not receive local Vancomycin antibiotic powder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Clinically Significant Deep Surgical Site Infection (SSI)	The main outcome will be the presence of clinically significant surgical site infection (SSI) in the first 26 weeks after surgery, as determined by CDC guidelines. The CDC criteria is currently 3 months for surgical site infection. To help capture more infections the study investigators have moved the time frame back to 6 months. Wound characteristics will also be evaluated using the ASEPSIS score. In this system wounds are scored using the weighted sum of points assigned for predetermined criteria including the need for Additional treatment, presence of Serous drainage, Erythema, Purulent exudates, Separation of deep tissues, the Isolation of bacteria, and the duration of patients Stay (ASEPSIS). The study investigators will define deep infections as those that require operative treatment, and superficial infections as those that are treated without operative intervention.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial Antibiotic Resistance Rate of Infected Participants	Secondary outcome measures in this study include culture data in the group that becomes infected. Sensitivities of the isolate determined routinely in current clinical practice, will be recorded for analysis. The most common bacterial isolates in infection after orthopaedic fracture care are methicillin resistant staph. aureus and methicillin resistant coagulase negative Staphylococci. The rate of bacterial Vancomycin sensitivity will be measured and analyzed.	26 weeks
Identify Risk Factors for Infection	A secondary outcome measure will be to determine the risk for postoperative infection as well as determine which patients are most likely to benefit from the local Vancomycin powder technique. Demographic variables will include age, presence of co-morbidities such as diabetes, smoking history, history of prior musculoskeletal infection, and history of infection within the past 30 days. Injury descriptors will include injury mechanism, open or closed fracture type, AO classification of the fracture type, other orthopaedic injuries, and other non-orthopaedic injuries. Treatment parameters will include time from injury to definitive treatment, time from injury to external fixation, and surgical approaches used.	26 weeks

Collaborators and Investigators

• Sponsor: Major Extremity Trauma Research Consortium
• Investigators: Principal Investigator: Robert O'Toole, MD, University of Maryland R Adams Cowley Shock Trauma Center; Study Director: Anthony Carlini, MS, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Major Extremity Trauma Research Consortium (METRC); O'Toole RV, Joshi M, Carlini AR, Murray CK, Allen LE, Huang Y, Scharfstein DO, O'Hara NN, Gary JL, Bosse MJ, Castillo RC, Bishop JA, Weaver MJ, Firoozabadi R, Hsu JR, Karunakar MA, Seymour RB, Sims SH, Churchill C, Brennan ML, Gonzales G, Reilly RM, Zura RD, Howes CR, Mir HR, Wagstrom EA, Westberg J, Gaski GE, Kempton LB, Natoli RM, Sorkin AT, Virkus WW, Hill LC, Hymes RA, Holzman M, Malekzadeh AS, Schulman JE, Ramsey L, Cuff JAN, Haaser S, Osgood GM, Shafiq B, Laljani V, Lee OC, Krause PC, Rowe CJ, Hilliard CL, Morandi MM, Mullins A, Achor TS, Choo AM, Munz JW, Boutte SJ, Vallier HA, Breslin MA, Frisch HM, Kaufman AM, Large TM, LeCroy CM, Riggsbee C, Smith CS, Crickard CV, Phieffer LS, Sheridan E, Jones CB, Sietsema DL, Reid JS, Ringenbach K, Hayda R, Evans AR, Crisco MJ, Rivera JC, Osborn PM, Kimmel J, Stawicki SP, Nwachuku CO, Wojda TR, Rehman S, Donnelly JM, Caroom C, Jenkins MD, Boulton CL, Costales TG, LeBrun CT, Manson TT, Mascarenhas DC, Nascone JW, Pollak AN, Sciadini MF, Slobogean GP, Berger PZ, Connelly DW, Degani Y, Howe AL, Marinos DP, Montalvo RN, Reahl GB, Schoonover CD, Schroder LK, Vang S, Bergin PF, Graves ML, Russell GV, Spitler CA, Hydrick JM, Teague D, Ertl W, Hickerson LE, Moloney GB, Weinlein JC, Zelle BA, Agarwal A, Karia RA, Sathy AK, Au B, Maroto M, Sanders D, Higgins TF, Haller JM, Rothberg DL, Weiss DB, Yarboro SR, McVey ED, Lester-Ballard V, Goodspeed D, Lang GJ, Whiting PS, Siy AB, Obremskey WT, Jahangir AA, Attum B, Burgos EJ, Molina CS, Rodriguez-Buitrago A, Gajari V, Trochez KM, Halvorson JJ, Miller AN, Goodman JB, Holden MB, McAndrew CM, Gardner MJ, Ricci WM, Spraggs-Hughes A, Collins SC, Taylor TJ, Zadnik M. Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial. JAMA Surg. 2021 May 1;156(5):e207259. doi: 10.1001/jamasurg.2020.7259. Epub 2021 May 12.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: August 21, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimate): August 28, 2014

Study Record Updates

• Last Update Posted (Actual): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Surgical site infection risk prevention; Bacterial species type and antibacterial sensitives
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Wound Infection; Infections; Communicable Diseases; Surgical Wound Infection; Anti-Infective Agents; Vancomycin; Anti-Bacterial Agents
• Other Study ID Numbers: W81XWH-10-2-0134