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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vancomycin Antibotic Powder | Experimental | 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. |
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| Standard of Care | No Intervention | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vancomycin antibiotic powder | Drug | At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure. |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pathogen Type | This secondary outcome represents the type of bacteria or fungus isolated from the fracture site at the time of surgery for infection during the follow up period. Cultures were obtained using routine clinical sterile technique in the operating room and processed according to standard laboratory practices at each participating site. An infectious disease physician blinded to treatment arm reviewed and categorized all culture results. Pathogens were classified into five groups: gram-positive cocci, gram-positive rods, gram-negative rods, anaerobes, and fungi. The frequency of each pathogen type recovered was compared between patients who received topical vancomycin powder during surgery and those who did not. |
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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:
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Renan Castillo, PhD | Johns Hopkins Bloomberg School of Public Health | Principal Investigator |
| Robert O'Toole, MD | University of Maryland R Adams Cowley Shock Trauma Center | Principal Investigator |
| Anthony Carlini, MS | Johns Hopkins Bloomberg School of Public Health | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland R Adams Cowley Shock Trauma Center | Baltimore | Maryland | 21201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41984450 | Derived | Major Extremity Trauma Research Consortium (METRC); O'Toole RV, O'Hara NN, Carlini AR, Schrank GM, Chung S, Gary JL, Obremskey W, Matuszewski PE, Teague D, Natoli RM, Gitajn IL, Weaver MJ, Renninger CH, Levack AE, Degani Y, Collins SC, Weston-Farber E, Howe AL, Thompson RE, Castillo RC, Karunakar MA, Blum L, Harmer L, Hsu JR, Kempton LB, Phelps KD, Seymour RB, Sims SH, Acharya MS, Callahan H, Chavez-Araujo LM, Churchill C, Gambuzza MP, Haim KR, Ishman E, Kendall JS, Mullis ND, Young C, Pilson HT, Carroll EA, Goodman JB, Holden MB, Jones AL, Moon C, Lin CA, Marecek GS, Moffitt GB, Conlan T, George AV, Fisher LA, Mullin DS, Recendez CL, Aneja A, Brameier DT, Heng M, Ly TV, Stenquist DS, Suneja N, Wignakumar T, Borgida JS, Policicchio TJ, Hanson GR, Alese OM, Ricci WM, Behrens SB, Dvorzhinskiy A, Bilodeau RE, Klinger CE, Mullis BH, Jang Y, Lopas LA, McKinley TO, O'Neill DC, Szatkowski JP, Virkus WW, Hill LC, Gaski G, Hymes RA, Ahn J, Goch AM, Holzman M, Malekzadeh AS, Schulman JE, Rivera JC, Krause PC, Bridgman C, Cohen J, Eikani C, Chavez M, Kudulis M, Warner SJ, Achor TS, Choo A, Eastman JG, Kellam PJ, Boutte SJ, Guevara KD, Reid KR, Vallier HA, Tucci AV, Davis JM, Bell AC, Bonyun ME, Healey K, Li V, McKibben NS, Nascone J, Okhuereigbe D, Sciadini MF, Slobogean G, Zingas N, Kovvur M, Lawrence JE, Phipps H, Rudnicki J, Turner KE, Hayda R, Evans AR, Quinnan S, Benitez A, Rehman S, Soderquist MC, Townsend CB, Caroom C, Collins AC, Okwumabua E, Shaikh HS, Spitler CA, Agarwal A, Johnson MD, Haller JM, Marchand LS, Alfonso NA, Gorman MA, Charlton WM, Scott BR, Kraus KM, Meredith SJ, Talwar S, Bergin PF, Jha AJ, McGee S, Nehete PV, Pryor TA, Spears I, Chen AT, Kelley B, Nez NR, Ertl WJ, Hull BR, Blumenthal S, Patterson JT, Flynn C, Ross RC, Agarwal A, Weiss DB, Hadeed MM, Yarboro SR, Daoud T, McVey ED, Whiting PS, Domes C, Goodspeed DC, Kuhn GR, Boyce R, Libos A, Mitchell PM, Moreno-Diaz AF, Ponce RB, Stinner DJ, Tatman LM, Velasco-Castro J, Trochez K, Satpathy J, Zuelzer DA, Potter BK. Intrawound Tobramycin Plus Vancomycin to Prevent Surgical Site Infection in Tibial Fractures: The TOBRA Randomized Clinical Trial. JAMA. 2026 May 12;335(18):1586-1595. doi: 10.1001/jama.2026.4023. |
| Label | URL |
|---|---|
| Related Info | View source |
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Approximately 1000 participants (500 per treatment arm) were enrolled across 36 METRC trauma centers over a 30-month period. Participants were recruited during the initial hospitalization for the their injury.
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| ID | Title | Description |
|---|---|---|
| FG000 | Control | Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder. |
| FG001 | Vancomycin Powder |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Oct 6, 2014 |
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| 26 weeks |
| Bacterial Susceptibility and Antimicrobial Resistance | This secondary outcome characterizes the susceptibility of recovered pathogens to commonly used antibiotics collected at the time of surgery for infection during follow up. Antimicrobial susceptibility testing was performed by hospital laboratories using standard methods at each participating site. The pattern of susceptibility and resistance to various antimicrobial agents was compared between the two treatment groups to assess whether exposure to topical vancomycin powder was associated with differences in antibiotic resistance profiles, including the emergence of resistant organisms or other hard-to-treat pathogens. | 26 weeks |
| 33760010 | Derived | 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. |
Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Vancomycin Antibiotic 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. Vancomycin antibiotic powder: At the time of fracture fixation 1000 mg of Vancomycin powder placed into the wound during wound closure. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean age (SD) in each study arm. | Numbers differ because each arm had a different number of participants. | Mean | Standard Deviation | years |
| |||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Units | surgical site infections | 26 weeks | surgical site infections | surgical site infections |
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| Secondary | Pathogen Type | This secondary outcome represents the type of bacteria or fungus isolated from the fracture site at the time of surgery for infection during the follow up period. Cultures were obtained using routine clinical sterile technique in the operating room and processed according to standard laboratory practices at each participating site. An infectious disease physician blinded to treatment arm reviewed and categorized all culture results. Pathogens were classified into five groups: gram-positive cocci, gram-positive rods, gram-negative rods, anaerobes, and fungi. The frequency of each pathogen type recovered was compared between patients who received topical vancomycin powder during surgery and those who did not. | Posted | Number | Count of pathogen type | 26 weeks |
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| Secondary | Bacterial Susceptibility and Antimicrobial Resistance | This secondary outcome characterizes the susceptibility of recovered pathogens to commonly used antibiotics collected at the time of surgery for infection during follow up. Antimicrobial susceptibility testing was performed by hospital laboratories using standard methods at each participating site. The pattern of susceptibility and resistance to various antimicrobial agents was compared between the two treatment groups to assess whether exposure to topical vancomycin powder was associated with differences in antibiotic resistance profiles, including the emergence of resistant organisms or other hard-to-treat pathogens. | Posted | Number | Infections (Gram positive sensitivities) | 26 weeks |
|
36 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder. | 3 | 499 | 21 | 499 | 0 | 499 |
| EG001 | Vancomycin Powder | Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder. | 4 | 481 | 16 | 481 | 0 | 481 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | Systematic Assessment |
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| Abdominal injury | Gastrointestinal disorders | Systematic Assessment |
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| Venous thromboembolism (VTE) | Blood and lymphatic system disorders | Systematic Assessment |
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| Nonunion | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Manipulation under anesthesia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Amputation | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Hip fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Abnormal laboratory values | General disorders | Systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Reaction to antibiotic | General disorders | Systematic Assessment |
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| Renal failure | Hepatobiliary disorders | Systematic Assessment |
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| Seizure | General disorders | Systematic Assessment |
| ||
| Thoracic injury | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Susan Collins | METRC | 4105028966 | scolli21@jhu.edu |
| May 6, 2021 |
| Prot_ICF_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 4, 2020 | Feb 22, 2021 | SAP_001.pdf |
| Male |
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| Non-Hispanic White |
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| Non-Hispanic Black |
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| Other |
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| Refused/Unknown |
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| Gram positive deep SSI |
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| Gram negative deep SSI |
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| Anerobe/fungal deep SSI |
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| Contaminated sample |
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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.
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