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

Primary Purpose

Post Operative Surgical Site Infection

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Vancomycin antibiotic powder
Sponsored by
Major Extremity Trauma Research Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post Operative Surgical Site Infection focused on measuring Surgical site infection risk prevention, Bacterial species type and antibacterial sensitives

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Maryland R Adams Cowley Shock Trauma Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Vancomycin Antibotic Powder

Standard of Care

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
August 21, 2014
Last Updated
May 6, 2021
Sponsor
Major Extremity Trauma Research Consortium
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1. Study Identification

Unique Protocol Identification Number
NCT02227446
Brief Title
Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO)
Acronym
VANCO
Official Title
Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (Vancomycin Study)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
June 2018 (Actual)
Study Completion Date
November 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Major Extremity Trauma Research Consortium

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Operative Surgical Site Infection
Keywords
Surgical site infection risk prevention, Bacterial species type and antibacterial sensitives

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1036 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vancomycin Antibotic Powder
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vancomycin antibiotic powder
Intervention Description
At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure.
Primary Outcome Measure Information:
Title
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Description
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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Bacterial Antibiotic Resistance Rate of Infected Participants
Description
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.
Time Frame
26 weeks
Title
Identify Risk Factors for Infection
Description
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.
Time Frame
26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renan Castillo, PhD
Organizational Affiliation
Johns Hopkins Bloomberg School of Public Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert O'Toole, MD
Organizational Affiliation
University of Maryland R Adams Cowley Shock Trauma Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anthony Carlini, MS
Organizational Affiliation
Johns Hopkins Bloomberg School of Public Health
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland R Adams Cowley Shock Trauma Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33760010
Citation
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.
Results Reference
derived
Links:
URL
http://metrc.org
Description
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Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO)

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