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

Major Extremity Trauma Research Consortium

Status and phase: Completed; Phase 3

Conditions: Post Operative Surgical Site Infection

Treatments: Drug: Vancomycin antibiotic powder

Study type: Interventional

Funder types: Other

Identifiers

NCT02227446

W81XWH-10-2-0134

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,036 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,036 participants in 2 patient groups

Vancomycin Antibotic Powder

Experimental group

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.

Treatment:

Drug: Vancomycin antibiotic powder

Standard of Care

No Intervention group

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.