Pre-operative Alcohol Skin Solutions in Fractured Extremities (PREPARE)

PREPARE: A Pragmatic Randomized Trial Evaluating Pre-operative Alcohol Skin Solutions in FRactured Extremites

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Surgical Site Infection; Pelvic Fracture; Unplanned Fracture-Related Reoperation; Open Appendicular Fracture; Closed Lower Extremity Fracture
• Intervention / Treatment: Drug: DuraPrep; Drug: ChloraPrep

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.

• Study Type: Interventional
• Enrollment (Anticipated): 8000
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada
      • Royal Columbia Hospital
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton Health Sciences
    • Hamilton, Ontario, Canada
      • McMaster University, Center for Evidence-Based Orthopaedics
• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90048
      • Cedars Sinai
    • San Jose, California, United States, 95126
      • Regional Medical Center of San Jose
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Methodist Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70803
      • Louisiana State University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, R Adams Cowley Shock Trauma Center
    • Cheverly, Maryland, United States, 20785
      • University of Maryland Capital Region Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan Health
  • New Hampshire
    • Hanover, New Hampshire, United States, 03755
      • Dartmouth-Hitchcock Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center, Atrium Health Musculoskeletal Institute
    • Durham, North Carolina, United States, 27708
      • Duke University Hospital
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44109
      • Case Western / MetroHealth Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117
      • Sanford Health
  • Texas
    • San Antonio, Texas, United States, 78234
      • San Antonio Military Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Health System Foundation / Inova Fairfax Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First pre-op antiseptic skin solution; The PREPARE trial will compare the most common alcohol-based pre-operative antiseptic skin solutions used during extremity fracture surgery. Participant recruitment will begin with the clinical sites using their assigned pre-operative antiseptic skin solution for all eligible fracture surgeries for a two-month period.	Drug: DuraPrep; The iodine-based treatment intervention is an antiseptic solution comprised of iodine povacrylex (0.7% free iodine) in 74% isopropyl alcohol. 3M™ DuraPrep™ [3M Health Care, St Paul, MN], will be the commercial product used.; Drug: ChloraPrep; The CHG intervention is an antiseptic solution comprised of 2% CHG in 70% isopropyl alcohol. ChloraPrep® [CareFusion Inc., Leawood, KS, USA] will be the product used.
Experimental: Crossover - Second pre-op antiseptic skin solution; 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 eligible fracture surgeries for a two-month period, and will then crossover back to the solution in the first intervention phase.	Drug: DuraPrep; The iodine-based treatment intervention is an antiseptic solution comprised of iodine povacrylex (0.7% free iodine) in 74% isopropyl alcohol. 3M™ DuraPrep™ [3M Health Care, St Paul, MN], will be the commercial product used.; Drug: ChloraPrep; The CHG intervention is an antiseptic solution comprised of 2% CHG in 70% isopropyl alcohol. ChloraPrep® [CareFusion Inc., Leawood, KS, USA] will be the product used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Site Infection: Superficial Incisional	Guided by the CDC's National Healthcare Safety Network reporting criteria	Within 30 days of the patient's last planned fracture management surgery
Surgical Site Infection: Deep Incision or Organ/Space	Guided by the CDC's National Healthcare Safety Network reporting criteria	Within 90 days of the patient's last planned fracture management surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within 12 months of the patient's last planned operation

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Patient-Centered Outcomes Research Institute; McMaster University
• Investigators: Principal Investigator: Gerard Slobogean, MD, University of Maryland Shock Trauma Center; Principal Investigator: Sheila Sprague, PhD, McMaster University; Principal Investigator: Mohit Bhandari, MD, McMaster University

Publications and helpful links

General Publications

• 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. Erratum In: Trials. 2020 Sep 30;21(1):821.
• 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. Erratum In: JAMA Netw Open. 2020 Sep 1;3(9):e2021571. JAMA Netw Open. 2021 Jun 1;4(6):e2117240.

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2018
• Primary Completion (Actual): March 15, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: May 10, 2018
• First Posted (Actual): May 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Surgical Site Infection; Open Fracture; Peri-operative Preparation Solutions; Lower Extremity Fracture; Pelvis; Fracture; DuraPrep; ChloraPrep
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Postoperative Complications; Wounds and Injuries; Leg Injuries; Femoral Fractures; Hip Injuries; Wound Infection; Fractures, Bone; Hip Fractures; Surgical Wound Infection
• Other Study ID Numbers: HP-00080639

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes