Trial Outcomes & Findings for Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter Randomized, Controlled Trial (VANCO) (NCT NCT02227446)
NCT ID: NCT02227446
Last Updated: 2021-06-01
Results Overview
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.
COMPLETED
PHASE3
1036 participants
26 weeks
2021-06-01
Participant Flow
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.
Participant milestones
| Measure |
Control
Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder.
|
Vancomycin Powder
Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder.
|
|---|---|---|
|
Overall Study
STARTED
|
521
|
515
|
|
Overall Study
COMPLETED
|
499
|
481
|
|
Overall Study
NOT COMPLETED
|
22
|
34
|
Reasons for withdrawal
| Measure |
Control
Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder.
|
Vancomycin Powder
Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder.
|
|---|---|---|
|
Overall Study
not eligible post randomization
|
18
|
29
|
|
Overall Study
Withdrawal by Subject
|
4
|
5
|
Baseline Characteristics
Numbers differ because each arm had a different number of participants.
Baseline characteristics by cohort
| Measure |
Vancomycin Antibiotic Powder
n=481 Participants
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.
|
Standard of Care
n=499 Participants
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.
|
Total
n=980 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.4 years
STANDARD_DEVIATION 14 • n=5 Participants • Numbers differ because each arm had a different number of participants.
|
46.1 years
STANDARD_DEVIATION 13.5 • n=7 Participants • Numbers differ because each arm had a different number of participants.
|
45.75 years
STANDARD_DEVIATION 13.8 • n=5 Participants • Numbers differ because each arm had a different number of participants.
|
|
Sex: Female, Male
Female
|
182 Participants
n=5 Participants
|
181 Participants
n=7 Participants
|
363 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
299 Participants
n=5 Participants
|
318 Participants
n=7 Participants
|
617 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
49 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic White
|
339 Participants
n=5 Participants
|
346 Participants
n=7 Participants
|
685 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic Black
|
71 Participants
n=5 Participants
|
77 Participants
n=7 Participants
|
148 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
19 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Refused/Unknown
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 26 weeksThe 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.
Outcome measures
| Measure |
Vancomycin Antibotic Powder
n=481 surgical site infections
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.
|
Standard of Care
n=499 surgical site infections
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.
|
|---|---|---|
|
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Total deep Surgical Site Infections
|
29 surgical site infections
|
48 surgical site infections
|
|
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Culture negative deep SSI
|
1 surgical site infections
|
1 surgical site infections
|
|
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Gram positive deep SSI
|
17 surgical site infections
|
36 surgical site infections
|
|
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Gram negative deep SSI
|
11 surgical site infections
|
10 surgical site infections
|
|
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Anerobe/fungal deep SSI
|
1 surgical site infections
|
0 surgical site infections
|
|
Number of Clinically Significant Deep Surgical Site Infection (SSI)
Contaminated sample
|
0 surgical site infections
|
1 surgical site infections
|
SECONDARY outcome
Timeframe: 26 weeksSecondary outcome measures in this study include culture data in the group that becomes infected. Sensitivities of the isolate determined routinely in current clinical practice, will be recorded for analysis. The most common bacterial isolates in infection after orthopaedic fracture care are methicillin resistant staph. aureus and methicillin resistant coagulase negative Staphylococci. The rate of bacterial Vancomycin sensitivity will be measured and analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 26 weeksA secondary outcome measure will be to determine the risk for postoperative infection as well as determine which patients are most likely to benefit from the local Vancomycin powder technique. Demographic variables will include age, presence of co-morbidities such as diabetes, smoking history, history of prior musculoskeletal infection, and history of infection within the past 30 days. Injury descriptors will include injury mechanism, open or closed fracture type, AO classification of the fracture type, other orthopaedic injuries, and other non-orthopaedic injuries. Treatment parameters will include time from injury to definitive treatment, time from injury to external fixation, and surgical approaches used.
Outcome measures
Outcome data not reported
Adverse Events
Control
Vancomycin Powder
Serious adverse events
| Measure |
Control
n=499 participants at risk
Participants randomized to the control arm received standard infection prevention protocol without 1000 mg of intrawound vancomycin powder.
|
Vancomycin Powder
n=481 participants at risk
Participants randomized to the intervention arm received standard infection prevention protocol with 1000 mg of intrawound vancomycin powder.
|
|---|---|---|
|
Infections and infestations
Infection
|
1.2%
6/499 • Number of events 6 • 36 months
|
0.62%
3/481 • Number of events 3 • 36 months
|
|
Gastrointestinal disorders
Abdominal injury
|
0.20%
1/499 • Number of events 1 • 36 months
|
1.0%
5/481 • Number of events 5 • 36 months
|
|
Blood and lymphatic system disorders
Venous thromboembolism (VTE)
|
0.60%
3/499 • Number of events 3 • 36 months
|
0.62%
3/481 • Number of events 3 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Nonunion
|
0.40%
2/499 • Number of events 2 • 36 months
|
0.42%
2/481 • Number of events 2 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Manipulation under anesthesia
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.42%
2/481 • Number of events 2 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Amputation
|
0.40%
2/499 • Number of events 2 • 36 months
|
0.00%
0/481 • 36 months
|
|
Musculoskeletal and connective tissue disorders
Hip fracture
|
0.00%
0/499 • 36 months
|
0.21%
1/481 • Number of events 1 • 36 months
|
|
General disorders
Abnormal laboratory values
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.00%
0/481 • 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.00%
0/481 • 36 months
|
|
General disorders
Reaction to antibiotic
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.00%
0/481 • 36 months
|
|
Hepatobiliary disorders
Renal failure
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.00%
0/481 • 36 months
|
|
General disorders
Seizure
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.00%
0/481 • 36 months
|
|
Respiratory, thoracic and mediastinal disorders
Thoracic injury
|
0.20%
1/499 • Number of events 1 • 36 months
|
0.00%
0/481 • 36 months
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place