Pre-operative Alcohol Skin Solutions in Fractured Extremities

NCT03523962 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: HP-00080639
• Study Type: interventional
• Target: 8,485
• Locations: 2 countries
• Sites: 27

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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Within 30 days of the patient's last planned fracture management surgery

• Number of Participants With a Deep Incisional 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

  Within 90 days of the patient's last planned fracture management surgery

Secondary Outcomes (1)

• Number of Participants With an Unplanned Fracture-Related Reoperation

  Within 12 months of the patient's last planned operation

Study Arms (2)

First pre-op antiseptic skin solution

EXPERIMENTAL

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; Drug: ChloraPrep

Crossover - Second pre-op antiseptic skin solution

EXPERIMENTAL

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; Drug: ChloraPrep

Interventions

DuraPrep DRUG

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.

Crossover - Second pre-op antiseptic skin solution; First pre-op antiseptic skin solution

ChloraPrep DRUG

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.

Crossover - Second pre-op antiseptic skin solution; First pre-op antiseptic skin solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years of age or older.
• Open fracture of the appendicular skeleton.
• Received or will receive definitive fracture treatment with a surgical implant(s) (i.e., internal fixation, external fixation, joint prosthesis, etc.).
• Open fracture wound management that includes formal surgical debridement within 72 hours of their injury.
• Will have all planned fracture care surgeries performed by a participating surgeon or delegate.
• Informed consent obtained.
• Patient enrolled within 3 weeks of their fracture.

You may not qualify if:

• Fracture of the hand (distal to radial carpal joint).
• Patients who did not or will not receive the allocated pre-operative surgical preparation solution due to a medical contraindication.
• Received previous surgical debridement or management of their fracture at a nonparticipating hospital or clinic (as applicable).
• Open fracture managed outside of the participating orthopaedic service (e.g., foot fracture managed by podiatrist).
• Chronic or acute infection at or near the fracture site at the time of initial fracture surgery.
• Burns at the fracture site.
• Incarceration.
• Expected injury survival of less than 90 days.
• Terminal illness with expected survival less than 90 days.
• Currently enrolled in a study that does not permit co-enrollment.
• Unable to obtain informed consent due to language barriers.
• Likely problems, in the judgment of study personnel, with maintaining follow-up with the patient.
• Prior or current enrollment in a PREP-IT trial.
• Enrolled in the PREPARE closed cohort.
• Excluded due to sampling strategy.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• McMaster University: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (27)

University of California, Irvine

Irvine, California, 92697, United States

Location

Cedars Sinai

Los Angeles, California, 90048, United States

Location

Regional Medical Center of San Jose

San Jose, California, 95126, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Louisiana State University

Baton Rouge, Louisiana, 70803, United States

Location

University of Maryland, R Adams Cowley Shock Trauma Center

Baltimore, Maryland, 21201, United States

Location

University of Maryland Capital Region Health

Cheverly, Maryland, 20785, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Bryan Health

Lincoln, Nebraska, 68506, United States

Location

Dartmouth-Hitchcock Medical Center

Hanover, New Hampshire, 03755, United States

Location

Carolinas Medical Center, Atrium Health Musculoskeletal Institute

Charlotte, North Carolina, 28203, United States

Location

Duke University Hospital

Durham, North Carolina, 27708, United States

Location

Wake Forest Baptist University Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

Case Western / MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Sanford Health

Sioux Falls, South Dakota, 57117, United States

Location

San Antonio Military Medical Center

San Antonio, Texas, 78234, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Inova Health System Foundation / Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

University of Wisconsin

Madison, Wisconsin, 53715, United States

Location

Royal Columbia Hospital

New Westminster, British Columbia, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, Canada

Location

McMaster University, Center for Evidence-Based Orthopaedics

Hamilton, Ontario, Canada

Location

Related Publications (4)

• PREP-IT Investigators; Sprague S, Slobogean G, Wells JL, O'Hara NN, Thabane L, Mullins CD, Harris AD, Wood A, Viskontas D, Apostle KL, O'Toole RV, Joshi M, Johal H, Al-Asiri J, Hymes RA, Gaski GE, Pilson HT, Carroll EA, Babcock S, Halvorson JJ, Romeo NM, Matson CA, Higgins TF, Marchand LS, Bergin PF, Morellato J, Van Demark RE 3rd, Potter GD, Gitajn IL, Chang G, Phelps KD, Kempton LB, Karunakar M, Jaeblon T, Demyanovich HK, Domes CM, Kuhn GR, Reilly RM, Gage MJ, Weaver MJ, von Keudell AG, Heng M, McTague MF, Alnasser A, Mehta S, Donegan DJ, Natoli RM, Szatkowski J, Scott AN, Shannon SF, Jeray KJ, Tanner SL, Marmor MT, Matityahu A, Fowler JT, Pierrie SN, Beltran MJ, Thomson CG, Lin CA, Moon CN, Scolaro JA, Amirhekmat A, Leonard J, Pogorzelski D, Bzovsky S, Heels-Ansdell D, Szasz OP, Gallant JL, Della Rocca GJ, Zura RD, Hebden JN, Patterson JT, Lee C, O'Hara LM, Marvel D, Palmer JE, Friedrich J, D'Alleyrand JG, Rivera JC, Mossuto F, Schrank GM, Guyatt G, Devereaux PJ, Bhandari M; The PREP-IT Investigators. Skin Antisepsis before Surgical Fixation of Extremity Fractures. N Engl J Med. 2024 Feb 1;390(5):409-420. doi: 10.1056/NEJMoa2307679.

  PMID: 38294973 DERIVED

• Boissonneault A, O Hara N, Pogorzelski D, Marchand L, Higgins T, Gitajn L, Gage MJ, Natoli RM, Sharma I, Pierrie S, O'Toole RV, Sprague S, Slobogean G; PREP-IT Investigators*. The impact of heterotopic ossification prophylaxis after surgical fixation of acetabular fractures: national treatment patterns and related outcomes. Injury. 2023 Mar 6:S0020-1383(23)00197-3. doi: 10.1016/j.injury.2023.03.001. Online ahead of print.

  PMID: 37002119 DERIVED

• 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.

  PMID: 32787892 DERIVED

• 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.

  PMID: 32259266 DERIVED

MeSH Terms

Conditions

Surgical Wound Infection; Hip Fractures; Fractures, Open

Interventions

DuraPrep

Condition Hierarchy (Ancestors)

Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Femoral Fractures; Fractures, Bone; Wounds and Injuries; Hip Injuries; Leg Injuries

Limitations and Caveats

1. The patients and their surgeons were aware of the trial-group assignments. 2. The trial was limited to patients undergoing surgery for a fracture, so the generalizability of these findings to other surgical populations is unknown.

Results Point of Contact

• Title: Research Administrator
• Organization: University of Maryland, Baltimore

ahowe@som.umaryland.edu

410-706-6823

Study Officials

• Gerard Slobogean, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

• Sheila Sprague, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Mohit Bhandari, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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 iodine povacrylex, 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Orthopaedics

Model Details: 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.

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: May 14, 2018
• Study Start: August 21, 2018
• Primary Completion: March 15, 2023
• Study Completion: February 2, 2024
• Last Updated: October 4, 2024
• Results First Posted: October 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (24); CA (3)