Trial Outcomes & Findings for Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA (NCT NCT04597008)
NCT ID: NCT04597008
Last Updated: 2026-07-22
Results Overview
Compare the proportion of deep SSIs of the study injury within 182 days of definitive fracture fixation surgery in patients treated with local Vancomycin powder compared to those treated with a combination of local Vancomycin and Tobramycin powders. For this study a "deep SSI" is a SSI that is treated with operative debridement. In the current CDC terminology this would include all deep organ space, deep incisional, and superficial infections that are treated with surgery.
COMPLETED
PHASE3
1660 participants
within 182 days of definitive fracture fixation surgery
2026-07-22
Participant Flow
The study was conducted at 39 trauma centers in the US between June 18, 2021, and January 31, 2025. Patients meeting inclusion and exclusion crtieria were screened and approached by the research team at each trauma center. All patients or their legally authorized representatives provided signed informed consent.
A total of 2310 patients were screened and a total of 1528 were adjudicated as eligible and included in the primary analysis.
Participant milestones
| Measure |
Control
Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
Treatment
Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
|---|---|---|
|
Overall Study
STARTED
|
775
|
753
|
|
Overall Study
COMPLETED
|
775
|
753
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Topical Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: TOBRA
Baseline characteristics by cohort
| Measure |
Control
n=775 Participants
Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
Treatment
n=753 Participants
Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stafe of definitive fracture fixation.
|
Total
n=1528 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.3 Years
STANDARD_DEVIATION 13.8 • n=9 Participants
|
46.7 Years
STANDARD_DEVIATION 14.8 • n=27 Participants
|
47 Years
STANDARD_DEVIATION 14.3 • n=267 Participants
|
|
Sex: Female, Male
Female
|
307 Participants
n=9 Participants
|
296 Participants
n=27 Participants
|
603 Participants
n=267 Participants
|
|
Sex: Female, Male
Male
|
468 Participants
n=9 Participants
|
457 Participants
n=27 Participants
|
925 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
African American
|
146 Participants
n=9 Participants
|
131 Participants
n=27 Participants
|
277 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
7 Participants
n=9 Participants
|
6 Participants
n=27 Participants
|
13 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 Participants
n=9 Participants
|
6 Participants
n=27 Participants
|
13 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=9 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
White
|
525 Participants
n=9 Participants
|
492 Participants
n=27 Participants
|
1017 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
More than one race
|
80 Participants
n=9 Participants
|
101 Participants
n=27 Participants
|
181 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
Refused to report race
|
9 Participants
n=9 Participants
|
15 Participants
n=27 Participants
|
24 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
92 Participants
n=9 Participants
|
125 Participants
n=27 Participants
|
217 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic
|
675 Participants
n=9 Participants
|
622 Participants
n=27 Participants
|
1297 Participants
n=267 Participants
|
|
Race/Ethnicity, Customized
Refused to report
|
8 Participants
n=9 Participants
|
6 Participants
n=27 Participants
|
14 Participants
n=267 Participants
|
|
Fracture location
Tibial plateau
|
437 Participants
n=9 Participants
|
420 Participants
n=27 Participants
|
857 Participants
n=267 Participants
|
|
Fracture location
Tibial pilon
|
338 Participants
n=9 Participants
|
333 Participants
n=27 Participants
|
671 Participants
n=267 Participants
|
|
Open/closed Fracture
Open Fractures
|
155 Participants
n=9 Participants
|
147 Participants
n=27 Participants
|
302 Participants
n=267 Participants
|
|
Open/closed Fracture
Closed Fractures
|
620 Participants
n=9 Participants
|
606 Participants
n=27 Participants
|
1226 Participants
n=267 Participants
|
PRIMARY outcome
Timeframe: within 182 days of definitive fracture fixation surgeryPopulation: Randomization was stratified by clinical site and fracture location (ie, tibial plateau or tibial pilon). Between June 18, 2021, and January 31, 2025, a total of 2310 patients met the trial's eligibility criteria. Of these patients, 1660 provided informed consent and were randomized. A total of 1528 participants were adjudicated as eligible and included in the primary analysis.
Compare the proportion of deep SSIs of the study injury within 182 days of definitive fracture fixation surgery in patients treated with local Vancomycin powder compared to those treated with a combination of local Vancomycin and Tobramycin powders. For this study a "deep SSI" is a SSI that is treated with operative debridement. In the current CDC terminology this would include all deep organ space, deep incisional, and superficial infections that are treated with surgery.
Outcome measures
| Measure |
Control
n=775 Participants
Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
Treatment
n=753 Participants
Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
|---|---|---|
|
Number of Participants With Deep Surgical Site Infection (SSI)
|
47 Participants
|
51 Participants
|
Adverse Events
Control
Treatment
Serious adverse events
| Measure |
Control
n=775 participants at risk
Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
Treatment
n=753 participants at risk
Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stafe of definitive fracture fixation.
|
|---|---|---|
|
Endocrine disorders
Kidney Insufficiency
|
0.13%
1/775 • up to 12 month since definitive fixation
Kidney insufficiency reported as serious adverse event. Kidney insufficiency was assessed while in-hospital and at each clinical follow-up by the site and reviewed by the medical monitor.
|
0.13%
1/753 • up to 12 month since definitive fixation
Kidney insufficiency reported as serious adverse event. Kidney insufficiency was assessed while in-hospital and at each clinical follow-up by the site and reviewed by the medical monitor.
|
Other adverse events
| Measure |
Control
n=775 participants at risk
Standard of Care + Local Vancomycin: Participants in the control group will receive a dose of 1000mg of Vancomycin powder in their wound bed, which is placed right before wound closure at the final stage of definitive fracture fixation.
|
Treatment
n=753 participants at risk
Standard of Care + Local Vancomycin + Local Tobramycin: Participants in the treatment group will receive a dose of 1000mg of Vancomycin powder AND a dose of 1200mg of Tobramycin powder in their wound bed, which is placed right before wound closure at the final stafe of definitive fracture fixation.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Nonunion
|
5.4%
42/775 • up to 12 month since definitive fixation
Kidney insufficiency reported as serious adverse event. Kidney insufficiency was assessed while in-hospital and at each clinical follow-up by the site and reviewed by the medical monitor.
|
4.6%
35/753 • up to 12 month since definitive fixation
Kidney insufficiency reported as serious adverse event. Kidney insufficiency was assessed while in-hospital and at each clinical follow-up by the site and reviewed by the medical monitor.
|
Additional Information
Research Project Director
Johns Hopkins Bloomberg School of Public Health
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place