Clinical trial NCT02227446: Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Operative Surgical Site Infection
Keywords: Surgical site infection risk prevention
Bacterial species type and antibacterial sensitives
Lead sponsor: Major Extremity Trauma Research Consortium
Sponsor class: OTHER
First posted: 2014-08-28
Enrollment: 1036
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Clinically Significant Deep Surgical Site Infection (SSI)
timeFrame: 26 weeks
Secondary outcomes:
measure: Bacterial Antibiotic Resistance Rate of Infected Participants
timeFrame: 26 weeks
measure: Identify Risk Factors for Infection
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland R Adams Cowley Shock Trauma Center
state: Maryland
Study officials:
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Renan Castillo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland R Adams Cowley Shock Trauma Center
name: Robert O'Toole, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Anthony Carlini, MS
role: STUDY_DIRECTOR
References:
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.