Open Appendicular Fracture, Surgical Site Infection, Unplanned Fracture-Related Reoperation
Conditions
Keywords
Surgical Site Infection, Open Fracture, Povidone-iodine, Chlorhexidine gluconate, Peri-operative Preparation Solutions
Brief summary
The prevention of infection is the single most important goal influencing peri-operative care of patients with open fractures. Standard practice in the management of open fractures includes sterile technique and pre-operative skin preparation with an antiseptic solution. The available solutions kill bacteria and decrease the quantity of native skin flora, thereby decreasing surgical site infection (SSI). While there is extensive guidance on specific procedures for prophylactic antibiotic use and standards for sterile technique, the evidence regarding the choice of antiseptic skin preparation solution is very limited for open fracture surgery.
Interventions
DRUG10% povidone-iodine (1% free iodine) in purified water
Participant recruitment will begin with the clinical sites using their assigned pre-operative antiseptic skin solution for all open fracture surgeries for a two-month period.
DRUG4% chlorhexidine gluconate (CHG) in purified water
Once the first intervention phase is completed, each site will crossover to the opposite study solution. Each site will need to develop local procedures to ensure a successful crossover. They will use the second solution for all open fracture surgeries for a two-month period, and will then crossover back to the solution in the first intervention phase.
Sponsors
McMaster University
United States Department of Defense
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The orthopaedic team (including the study coordinators) cannot be blinded to the treatment allocation as the antiseptic solutions are visually distinguishable and these individuals need to lead the implementation of the cluster-crossover protocol at their clinical site. The Adjudication Committee Members and data analysts will be blinded to the study treatment. All interpretation of study results will initially be done in a blinded manner by developing two interpretations of the results. One interpretation will assume treatment A is povidone-iodine, the other interpretation will assume it is CHG. Once the data interpretations for each assumption are finalized, the data will be unblinded and the correct interpretation will be accepted.
Intervention model description
Treatment allocation will be determined using a cluster-randomized crossover trial design. The order of treatment allocation for each orthopaedic practice will be randomly assigned using a computer generated randomization table. Each site will start with the initially allocated study solution and eventually crossover to the other solution for their second recruitment period. This process of alternating treatments will repeat approximately every 2 months as dictated by the initial randomization.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The inclusion criteria are: 1. Patients 18 years of age or older. 2. Open fracture of the appendicular skeleton. 3. Received or will receive definitive fracture treatment with a surgical implant(s) (e.g., internal fixation, external fixation, joint prosthesis, etc.). 4. Open fracture wound management that includes formal surgical debridement within 72 hours of their injury. 5. Will have all planned fracture care surgeries performed by a participating surgeon or delegate. 6. Informed consent obtained. 7. Patient enrolled within 3 weeks of their fracture. The
Exclusion criteria
are: 1. Patients that did not or will not receive the allocated pre-operative surgical preparation solution due to a medical contraindication. 2. Received previous surgical debridement or management of their open fracture at a non-participating hospital or clinic. 3. Open fracture managed outside of the participating orthopaedic service (e.g., hand fracture managed by plastic surgeon). 4. Chronic or acute infection at or near the fracture site at the time of initial fracture surgery. 5. Burns at the fracture site. 6. Incarceration. 7. Expected injury survival of less than 90 days. 8. Terminal illness with expected survival less than 90 days. 9. Previous enrollment in a PREP-IT trial. 10. Currently enrolled in a study that does not permit co-enrollment. 11. Unable to obtain informed consent due to language barriers. 12. Likely problems, in the judgment of study personnel, with maintaining follow-up with the patient. 13. Excluded due to sampling strategy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Superficial Incisional Surgical Site Infection (SSI) | Within 30 days of the patient's last planned fracture management surgery | Guided by the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network reporting criteria (2017): Date of event for infection may occur from the date of fracture to 30 days after the definitive fracture management surgery; AND involves only skin and subcutaneous tissue of the incision; AND patient has at least one of the following: 1. purulent drainage from the superficial incision. 2. organisms identified from an aseptically obtained specimen from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment 3. superficial incision that is deliberately opened by a surgeon, and culture or non-culture-based testing is not performed. AND patient has at least one of the following signs or symptoms: pain or tenderness; localized swelling; erythema; or heat. 4. diagnosis of a superficial incisional SSI by the surgeon. |
| Number of Participants With a Deep Incisional or Organ/Space Infection | Within 90 days of the patient's last planned fracture management surgery | Guided by CDC's National Healthcare Safety Network Surgical Site Infection reporting criteria (2017): Deep Incisional Infection: Occurs within 90 days post definitive fracture management; & involves fascial/muscle layers; & has at least one of the following: 1. deep incision purulent drainage 2. a deep incision that dehisces, or is opened by a surgeon, and organism is identified by microbiologic testing; or microbiologic testing is not performed & has at least one of the following: fever (\> 38 °C); localized pain or tenderness 3. other evidence of deep incision infection on anatomical exam or imaging test Organ/Space Infection: Occurs within 90 days post definitive fracture management; & involves any part of the body deeper than the fascial/muscle layers; & has at least one of the following: 1. organ/space purulent drainage 2. organisms in organ/space identified by microbiologic testing 3. other evidence of organ/space infection on anatomical exam or imaging test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Unplanned Fracture-Related Reoperation | Within 12 months of the patient's last planned operation | Common examples include any unplanned fracture-related surgery that is associated with an infection at the operative site or contiguous to it, a wound-healing problem, or a fracture delayed union or non-union. |
Countries
Canada, Spain, United States
Participant flow
Recruitment details
Recruitment occurred between April 8, 2018, and June 8, 2021 at 14 hospitals in Canada, Spain and the USA. Eligible patients were adults aged 18 years or older with an open extremity fracture treated with a surgical fixation implant. For inclusion, the open fracture required formal surgical debridement within 72 hours of the injury.
Pre-assignment details
To ensure wide generalizability to routine practice, the protocol allowed prewashing of the operative extremity with alcohol or other antiseptics before performing the final skin antisepsis with the study solution. In addition to ensuring trial feasibility and protocol adherence, this decision pragmatically allowed the intact skin to receive mechanical scrubbing or partial alcohol antisepsis at the treating surgeon's discretion.
Participants by arm
| Arm | Count |
|---|---|
| 10% Povidone-iodine (1% Free Iodine) in Purified Water The povidone-iodine solution will contain 10% povidone-iodine (1% free iodine) in purified water as the only active ingredient. Operating room personnel will apply the solution to the operative site as the final preoperative skin antisepsis preparation immediately prior to commencing surgical fixation. They will apply the solution as per manufacturer's directions for use (e.g., technique of application, duration of application, drying time, drying techniques, replacement of draping, etc.).
10% povidone-iodine (1% free iodine) in purified water: Participant recruitment will begin with the clinical sites using their assigned pre-operative antiseptic skin solution for all open fracture surgeries for a two-month period.
4% chlorhexidine gluconate (CHG) in purified water: Once the first intervention phase is completed, each site will crossover to the opposite study solution. Each site will need to develop local procedures to ensure a successful crossover. They will use the second solution for all open fracture surgeries for a two-month period, and will then crossover back to the solution in the first intervention phase. | 828 |
| 4% Chlorhexidine Gluconate (CHG) in Purified Water The CHG solution will contain 4% CHG in purified water as the only active ingredient. Operating room personnel will apply the solution to the operative site as the final preoperative skin antisepsis preparation immediately prior to commencing surgical fixation. They will apply the solution as per manufacturer's directions (e.g., technique of application, duration of application, drying time, replacement of draping, etc.).
10% povidone-iodine (1% free iodine) in purified water: Participant recruitment will begin with the clinical sites using their assigned pre-operative antiseptic skin solution for all open fracture surgeries for a two-month period.
4% chlorhexidine gluconate (CHG) in purified water: Once the first intervention phase is completed, each site will crossover to the opposite study solution. Each site will need to develop local procedures to ensure a successful crossover. They will use the second solution for all open fracture surgeries for a two-month period, and will then crossover back to the solution in the first intervention phase. | 810 |
| Total | 1,638 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 19 | 7 |
| Overall Study | Incarceration | 2 | 3 |
| Overall Study | Lost to Follow-up | 17 | 14 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | 4% Chlorhexidine Gluconate (CHG) in Purified Water | Total | 10% Povidone-iodine (1% Free Iodine) in Purified Water |
|---|---|---|---|
| Age, Continuous Age | 44.5 years STANDARD_DEVIATION 17.9 | 44.9 years STANDARD_DEVIATION 18.1 | 45.2 years STANDARD_DEVIATION 18.2 |
| American Society of Anesthesiologist (ASA) Physical Score Class III or higher | 374 Participants | 779 Participants | 405 Participants |
| American Society of Anesthesiologist (ASA) Physical Score Class I or II | 436 Participants | 859 Participants | 423 Participants |
| BMI Healthy weight (18.5 - 24.9 kg/m^2) | 200 Participants | 443 Participants | 243 Participants |
| BMI Obesity (>30.0 kg/m^2) | 329 Participants | 658 Participants | 329 Participants |
| BMI Overweight (25.0-29.9 kg/m^2) | 271 Participants | 518 Participants | 247 Participants |
| BMI Underweight (<18.5 kg/m^2) | 10 Participants | 19 Participants | 9 Participants |
| Current smoker | 274 Participants | 567 Participants | 293 Participants |
| Diabetes of any type | 76 Participants | 170 Participants | 94 Participants |
| Number of included open fractures per participant One | 753 Participants | 1528 Participants | 775 Participants |
| Number of included open fractures per participant Three | 6 Participants | 15 Participants | 9 Participants |
| Number of included open fractures per participant Two | 51 Participants | 95 Participants | 44 Participants |
| Race/Ethnicity, Customized Race Asian | 10 Participants | 18 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Black | 137 Participants | 261 Participants | 124 Participants |
| Race/Ethnicity, Customized Race Central or South American | 20 Participants | 30 Participants | 10 Participants |
| Race/Ethnicity, Customized Race Indigenous | 5 Participants | 16 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Multiracial | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Prefer not to answer | 11 Participants | 18 Participants | 7 Participants |
| Race/Ethnicity, Customized Race White | 624 Participants | 1289 Participants | 665 Participants |
| Sex: Female, Male Female | 303 Participants | 627 Participants | 324 Participants |
| Sex: Female, Male Male | 507 Participants | 1011 Participants | 504 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 19 / 828 | 7 / 810 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 365 / 828 | 368 / 810 |
Outcome results
Primary
Number of Participants With a Deep Incisional or Organ/Space Infection
Guided by CDC's National Healthcare Safety Network Surgical Site Infection reporting criteria (2017): Deep Incisional Infection: Occurs within 90 days post definitive fracture management; & involves fascial/muscle layers; & has at least one of the following: 1. deep incision purulent drainage 2. a deep incision that dehisces, or is opened by a surgeon, and organism is identified by microbiologic testing; or microbiologic testing is not performed & has at least one of the following: fever (\> 38 °C); localized pain or tenderness 3. other evidence of deep incision infection on anatomical exam or imaging test Organ/Space Infection: Occurs within 90 days post definitive fracture management; & involves any part of the body deeper than the fascial/muscle layers; & has at least one of the following: 1. organ/space purulent drainage 2. organisms in organ/space identified by microbiologic testing 3. other evidence of organ/space infection on anatomical exam or imaging test
Time frame: Within 90 days of the patient's last planned fracture management surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10% Povidone-iodine (1% Free Iodine) in Purified Water | Number of Participants With a Deep Incisional or Organ/Space Infection | 46 Participants |
| 4% Chlorhexidine Gluconate (CHG) in Purified Water | Number of Participants With a Deep Incisional or Organ/Space Infection | 51 Participants |
Primary
Number of Participants With a Superficial Incisional Surgical Site Infection (SSI)
Guided by the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network reporting criteria (2017): Date of event for infection may occur from the date of fracture to 30 days after the definitive fracture management surgery; AND involves only skin and subcutaneous tissue of the incision; AND patient has at least one of the following: 1. purulent drainage from the superficial incision. 2. organisms identified from an aseptically obtained specimen from the superficial incision or subcutaneous tissue by a culture or non-culture based microbiologic testing method which is performed for purposes of clinical diagnosis or treatment 3. superficial incision that is deliberately opened by a surgeon, and culture or non-culture-based testing is not performed. AND patient has at least one of the following signs or symptoms: pain or tenderness; localized swelling; erythema; or heat. 4. diagnosis of a superficial incisional SSI by the surgeon.
Time frame: Within 30 days of the patient's last planned fracture management surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10% Povidone-iodine (1% Free Iodine) in Purified Water | Number of Participants With a Superficial Incisional Surgical Site Infection (SSI) | 13 Participants |
| 4% Chlorhexidine Gluconate (CHG) in Purified Water | Number of Participants With a Superficial Incisional Surgical Site Infection (SSI) | 7 Participants |
Secondary
Number of Participants With an Unplanned Fracture-Related Reoperation
Common examples include any unplanned fracture-related surgery that is associated with an infection at the operative site or contiguous to it, a wound-healing problem, or a fracture delayed union or non-union.
Time frame: Within 12 months of the patient's last planned operation
Population: Primary and secondary outcomes were evaluated using a complete case analysis. For that reason, the overall number of participants analyzed differs from the numbers provided under the Participant Flow module.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10% Povidone-iodine (1% Free Iodine) in Purified Water | Number of Participants With an Unplanned Fracture-Related Reoperation | 118 Participants |
| 4% Chlorhexidine Gluconate (CHG) in Purified Water | Number of Participants With an Unplanned Fracture-Related Reoperation | 115 Participants |