Clinical trial NCT03523962: Pre-operative Alcohol Skin Solutions in Fractured Extremities
Official title: PREPARE: A Pragmatic Randomized Trial Evaluating Pre-operative Alcohol Skin Solutions in FRactured Extremites
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Surgical Site Infection
Unplanned Fracture-Related Reoperation
Open Appendicular Fracture
Closed Lower Extremity Fracture
Pelvic Fracture
Keywords: Surgical Site Infection
Open Fracture
Lower Extremity Fracture
Pelvis; Fracture
DuraPrep
ChloraPrep
Peri-operative Preparation Solutions
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: McMaster University
name: Patient-Centered Outcomes Research Institute
First posted: 2018-05-14
Enrollment: 8485
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Treatment allocation will be determined using a cluster-randomized crossover trial design. The open and closed fracture populations will be treated with the same allocated solution at all times during the trial. 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.
Primary purpose: TREATMENT

Brief summary: The prevention of infection is an important goal influencing peri-operative care of extremity fracture patients. Standard practice in the operative management of extremity 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 extremity fracture surgery.

Detailed description: More than one million Americans suffer an extremity fracture (broken bone in the arm, leg, or pelvis) that requires surgery each year. Approximately 5% (or 50,000) of surgical fracture patients develop a surgical site infection (SSI), which is twice the rate among most surgical patients and nearly five times the rate among patients undergoing elective orthopaedic surgeries (e.g. joint replacement). Patients who develop a SSI after their fracture fixation surgery experience a long and difficult treatment pathway. Researchers have identified that when a fracture patient experiences a SSI, they typically undergo at least two additional surgeries to control the infection, spend a median of 14 additional days in the hospital, and have significantly lower health related quality of life (HRQL). Similarly, results from the recently completed Fluid Lavage of Open Wounds (FLOW) trial confirmed that patients who had a SSI, or another complication, that required an additional surgery reported significantly lower physical and mental HRQL in the 12 months following their fracture compared to patients who did not experience a SSI. In the most severe cases, when a SSI cannot be controlled, a limb amputation becomes necessary.

Open fractures, closed lower extremity fractures, and pelvic fractures represent some of the most severe musculoskeletal injuries. Due to their high-energy mechanisms, these fractures are often accompanied by soft-tissue injuries that contribute to unacceptably poor outcomes. The FLOW trial of 2,447 open fracture patients reported a 13.2% incidence of open fracture-related reoperations; Closed fractures of the lower extremity are also at high risk of complications, particularly when compared to closed upper extremity fractures. For example, the rate of SSI in closed tibial plateau and plafond fractures range from 5.6 - 11.9%, although some cohort studies have reported infection rates as high as 25.0%. This is contrast with SSI rates of \<5% for common upper extremity fractures like humeral shaft, forearm, or distal radius fractures. This is further illustrated in a series of 214 deep orthopaedic fracture infections, in which 58% occurred in the tibia and ankle, and only 10% occurred anywhere in the upper extremity. Finally, pelvic fractures are associated with some of the most challenging SSIs to treat among closed fractures because of their propensity to gram negative organisms and limitations in reconstruction options post-infection. Ultimately, infectious complications in these fracture populations lead to prolonged morbidity, loss of function, and potential limb loss.

Eligibility criteria: The open fracture 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) (i.e., 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 open fracture exclusion criteria are:

1. Fracture of the hand (distal to radial carpal joint).
2. Patients who did not or will not receive the allocated pre-operative surgical preparation solution due to a medical contraindication.
3. Received previous surgical debridement or management of their fracture at a nonparticipating hospital or clinic (as applicable).
4. Open fracture managed outside of the participating orthopaedic service (e.g., foot fracture managed by podiatrist).
5. Chronic or acute infection at or near the fracture site at the time of initial fracture surgery.
6. Burns at the fracture site.
7. Incarceration.
8. Expected injury survival of less than 90 days.
9. Terminal illness with expected survival less than 90 days.
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. Prior or current enrollment in a PREP-IT trial.
14. Enrolled in the PREPARE closed cohort.
15. Excluded due to sampling strategy.

The closed fracture inclusion criteria are:

1. Patients 18 years of age or older.
2. Closed fracture of the lower extremity or pelvis.
3. Received or will receive definitive fracture treatment with a surgical implant(s) (i.e., internal fixation, external fixation, joint prosthesis, etc.).
4. Fracture management requires a surgical incision (i.e., for fracture reduction or implant insertion).
5. Will have all planned fracture care surgeries performed by a participating surgeon or delegate.
6. Informed consent obtained.
7. Patient enrolled within 6 weeks of their fracture.

The closed fracture exclusion criteria are:

1. Patients who did not or will not receive the allocated pre-operative surgical preparation solution due to a medical contraindication.
2. Received previous surgical management of their fracture at a non-participating hospital or clinic.
3. Fracture managed outside of the participating orthopaedic service (e.g., foot fracture managed by podiatrist).
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. Currently enrolled in a study that does not permit co-enrollment.
10. Unable to obtain informed consent due to language barriers.
11. Likely, problems, in the judgment of study personnel, with maintaining follow-up with the patient.
12. Prior or current enrollment in a PREP-IT trial.
13. Enrolled in the PREPARE open cohort.
14. Excluded due to sampling strategy.

Primary outcomes:
measure: Number of Participants With a Superficial Incisional Surgical Site Infection (SSI)
timeFrame: Within 30 days of the patient's last planned fracture management surgery
measure: Number of Participants With a Deep Incisional Infection
timeFrame: Within 90 days of the patient's last planned fracture management surgery
Secondary outcomes:
measure: Number of Participants With an Unplanned Fracture-Related Reoperation
timeFrame: Within 12 months of the patient's last planned operation
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: San Jose
country: United States
facility: Regional Medical Center of San Jose
state: California
city: Indianapolis
country: United States
facility: Indiana University Health Methodist Hospital
state: Indiana
city: Baton Rouge
country: United States
facility: Louisiana State University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, R Adams Cowley Shock Trauma Center
state: Maryland
city: Cheverly
country: United States
facility: University of Maryland Capital Region Health
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Lincoln
country: United States
facility: Bryan Health
state: Nebraska
city: Hanover
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Charlotte
country: United States
facility: Carolinas Medical Center, Atrium Health Musculoskeletal Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Case Western / MetroHealth Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: San Antonio
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Health System Foundation / Inova Fairfax Hospital
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: New Westminster
country: Canada
facility: Royal Columbia Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University, Center for Evidence-Based Orthopaedics
state: Ontario
Study officials:
affiliation: University of Maryland, Baltimore
name: Gerard Slobogean, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Sheila Sprague, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Mohit Bhandari, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sprague S, Scott T, Dodds S, Pogorzelski D, McKay P, Harris AD, Wood A, Thabane L, Bhandari M, Mehta S, Gaski G, Boulton C, Marcano-Fernandez F, Guerra-Farfan E, Hebden J, O'Hara LM, Slobogean GP; PREP-IT Investigators. Cluster identification, selection, and description in cluster randomized crossover trials: the PREP-IT trials. Trials. 2020 Aug 12;21(1):712. doi: 10.1186/s13063-020-04611-9.
citation: Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) Investigators; Slobogean GP, Sprague S, Wells J, Bhandari M, Rojas A, Garibaldi A, Wood A, Howe A, Harris AD, Petrisor BA, Mullins DC, Pogorzelski D, Marvel D, Heels-Ansdell D, Mossuto F, Grissom F, Del Fabbro G, Guyatt GH, Della Rocca GJ, Demyanovich HK, Gitajn IL, Palmer J, D'Alleyrand JC, Friedrich J, Rivera J, Hebden J, Rudnicki J, Fowler J, Jeray KJ, Thabane L, Marchand L, O'Hara LM, Joshi MG, Talbot M, Camara M, Szasz OP, O'Hara NN, McKay P, Devereaux PJ, O'Toole RV, Zura R, Morshed S, Dodds S, Li S, Tanner SL, Scott T, Nguyen U. Effectiveness of Iodophor vs Chlorhexidine Solutions for Surgical Site Infections and Unplanned Reoperations for Patients Who Underwent Fracture Repair: The PREP-IT Master Protocol. JAMA Netw Open. 2020 Apr 1;3(4):e202215. doi: 10.1001/jamanetworkopen.2020.2215.