Prophylactic Antibiotic Coated Nail to Prevent Infection: A Clinical Trial

Study Overview
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Brief Summary
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This prospective randomized clinical trial will compare outcomes between patients treated primarily with a prophylactic antibiotic coated nail and those treated with traditional standard of care intramedullary (IM) nailing.

Detailed Description
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Despite significant treatment advances and protocols to prevent infection, severe open fractures of the lower extremity still have very high rates of deep infection. Infection in an active duty military population increases disability and decreases the likelihood of returning to duty. In addition, infection is one of the main factors associated with rehospitalization. Further, deep infections have not only resulted in increased disability after injury, infection is implicated as one of the main factors in late amputation. Among service members, only 20-25% with a severe open tibia fracture are able to return to active duty. Novel techniques for reducing infection are needed. The proposed study addresses the focus area of fracture-related infections, specifically the prevention of infection. This prospective randomized clinical trial will compare outcomes between patients treated primarily with a prophylactic antibiotic coated nail and those treated with traditional standard of care intramedullary (IM) nailing. This prospective randomized clinical trial will compare outcomes between patients treated primarily with a prophylactic antibiotic coated nail and those treated with traditional standard of care intramedullary (IM) nailing. The target population for the proposed study is patients with severe open tibia fractures (Type II or Type III) who require definitive fixation with intramedullary nail recruited from one of the participating sites during the index hospitalization. One group will be treated prophylactically using an antibiotic coated intramedullary nail at time of definitive fixation (1CN), while the second group will be treated with traditional standard of care intramedullary nail without antibiotic-coating (SN). Participant will be followed for 12 months (data capture including patient interviews and clinical data capture from the treatment team and medical record at baseline, 6 weeks, 3 months, 6 months, and 12 months).

Official Title
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Prophylactic Antibiotic Coated Nail to Prevent Infection: A Clinical Trial

Conditions
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Osteomyelitis Tibia, Tibial Fractures, Open Tibia Fracture

Intervention / Treatment
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* Drug: Antibiotic coated intramedullary Nail
* Other: Standard Intramedullary Nail


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years or older Gustilo Type II or III open tibia fracture requiring definitive fixation with intramedullary nail Exclusion Criteria: Less than 18 years of age Allergy to vancomycin or gentamicin Unable to speak English or Spanish Pregnant and lactating women Prisoner Unable to follow up for 12 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intramedullary Nail<br>Traditional standard of care intramedullary (IM) nail | Other: Standard Intramedullary Nail<br>* Standard Intramedullary Nail<br>|
| Active Comparator: Antibiotic Coated Intramedullary Nail<br>Intramedullary Nail coated with 2 grams of vancomycin and 560 mg gentamicin liquid. | Drug: Antibiotic coated intramedullary Nail<br>* Antibiotic coated intramedullary nail: A mixture of 40gm bag of acrylic cement, antibiotic powder (Vancomycin 2gm) and 560mg gentamicin liquid. The intramedullary is coated with the mixture using a cement gun tube.<br>* Other names: Vancomycin 2gm Liquid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who develop deep surgical site infection (SSI) | Number of participants in each group who develop SSI as defined by the criteria establish by the Centers for Disease Control and Prevention (CDC). The CDC criteria define deep as occurring within 30 or 90 days after the procedure. However, we will continue to follow patients for 12 months and document any infections and other complications during this period. | Day 30 through month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Union Scale in Tibial fractures (RUST) score | The RUST score ranges from a minimum score of 4 (definitely not healed) to a maximum score of 12 (completely healed). The final x-ray obtained within a 12-month period following injury will be uploaded to REDCap for review by a blinded panel of investigators from participating sites. | week 6, month 3, month 6, and month 12 | 
| Percentage of Union | Union is the gradual process of bone regeneration after a fracture. Percentage of Union, as determined by the treating surgeon, will be assessed via radiographs. Recorded by surgeon as yes/no answers. | week 6, month 3, month 6 and month12 | 
| Time to Union | Captured in days | week 6, month 3, month 6 and month12 | 
| Average Time to Return to Work/Duty | number of days | week 6, month 3, month 6 and month12 | 
| International Physical Activity Questionnaire (IPAQ) | IPAQ measures the total amount of physical activity completed in a 7 day period by calculating the minutes per week in in each physical activity level domain (walking, moderate and vigorous) by a metabolic equivalent energy (MET) expenditure estimate. Walking = 3.3 x number of walking minutes x number of walking days Moderate activity= 4.0 x number activity minutes x number of days Vigorous activity = 8 x number of activity minutes x number of days Total = Walking MET-min/wk+moderate MET-min/wk+vigorous MET-min/wk | week 6, month 3, month 6 and month12 | 
| Number of Subjects Who Have Returned to Work | Determined by asking whether subjects have returned to work | week 6, month 3, month 6 and month12 | 
| Number of Participants who Return to Operating Room (OR) |  | Month 12 | 
| PROMIS-29 Subscale--Physical Function | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means higher physical function. | week 6, month 3, month 6 and month12 | 
| PROMIS-29 Subscale--Physical Function: Anxiety | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of anxiety. | week 6, month 3, month 6 and month12 | 
| PROMIS-29 Subscale--Depression | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of depression. | week 6, month 3, month 6 and month12 | 
| PROMIS-29 Subscale--Fatigue | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of fatigue. | week 6, month 3, month 6 and month12 | 
| PROMIS-29 Subscale--Sleep Disturbance | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of sleep disturbance. | week 6, month 3, month 6 and month12 | 
| PROMIS-29 Subscale--Pain Interference | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of pain interference. | week 6, month 3, month 6 and month12 | 
| PROMIS-29 Subscale--Ability to Participate in Social Roles and Activities | The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher ability to participate in social roles and activities. | week 6, month 3, month 6 and month12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotic-coated nail