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Surgical Site InfectionPhase 4PREPARENCT03523962

Pre-operative Alcohol Skin Solutions in Fractured Extremities

A Phase 4 study testing DuraPrep and ChloraPrep in people with Surgical Site Infection and Unplanned Fracture-Related Reoperation, run by University of Maryland, Baltimore at 27 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DuraPrep and ChloraPrep
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8,485 participants
Where
27 sitesin 2 countries
Study dates
21 Aug 2018to 2 Feb 2024
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

27 sites in 2 countries.

27 sites in 2 countries

United States24 sites

  • University of Maryland, R Adams Cowley Shock Trauma Center

    Baltimore, Maryland, 21201

  • Louisiana State University

    Baton Rouge, Louisiana, 70803

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Carolinas Medical Center, Atrium Health Musculoskeletal Institute

    Charlotte, North Carolina, 28203

  • University of Maryland Capital Region Health

    Cheverly, Maryland, 20785

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • Case Western / MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Duke University Hospital

    Durham, North Carolina, 27708

  • Inova Health System Foundation / Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • Greenville Health System

    Greenville, South Carolina, 29605

  • Dartmouth-Hitchcock Medical Center

    Hanover, New Hampshire, 03755

  • Indiana University Health Methodist Hospital

    Indianapolis, Indiana, 46202

  • University of California, Irvine

    Irvine, California, 92697

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Bryan Health

    Lincoln, Nebraska, 68506

  • Cedars Sinai

    Los Angeles, California, 90048

  • University of Wisconsin

    Madison, Wisconsin, 53715

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Utah

    Salt Lake City, Utah, 84112

  • San Antonio Military Medical Center

    San Antonio, Texas, 78234

  • Regional Medical Center of San Jose

    San Jose, California, 95126

  • Sanford Health

    Sioux Falls, South Dakota, 57117

  • Wake Forest Baptist University Medical Center

    Winston-Salem, North Carolina, 27157

Other trials in United States

Canada3 sites

  • Hamilton Health Sciences

    Hamilton, Ontario

  • McMaster University, Center for Evidence-Based Orthopaedics

    Hamilton, Ontario

  • Royal Columbia Hospital

    New Westminster, British Columbia

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
DuraPrep, ChloraPrep
Keywords
Surgical Site Infection, Open Fracture, Lower Extremity Fracture, Pelvis; Fracture, DuraPrep, ChloraPrep, Peri-operative Preparation Solutions
Medical subject headings
Surgical Wound Infection, Hip Fractures, Fractures, Open

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DuraPrepDrug

    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.

  • ChloraPrepDrug

    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.

Study groups in NCT03523962
Study groupRoleWhat they receive
First pre-op antiseptic skin solutionExperimentalThe 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.
Receives: Drug: DuraPrep; Drug: ChloraPrep
Crossover - Second pre-op antiseptic skin solutionExperimentalOnce 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.
Receives: Drug: DuraPrep; Drug: ChloraPrep

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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

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

Secondary outcomes (1)

  1. 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.

    Measured: Within 12 months of the patient's last planned operation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2018
  2. Study start21 Aug 2018
  3. Primary completion15 Mar 2023
  4. Study completion2 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
8,485 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03523962
Sponsor's protocol ID
HP-00080639
Acronym
PREPARE
Status last verified
Sep 2024
First submitted
30 Apr 2018
Last updated
4 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38294973

  • 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; Executive Committee; Steering Committee; Adjudication Committee; Data and Safety Monitoring Committee; Research Methodology Core; Patient Centred Outcomes Core; Orthopaedic Surgery Core; Operating Room Core; Infectious Disease Core; Military Core; McMaster University Methods Center (Hamilton, ON); University of Maryland School of Medicine Administrative Center (Baltimore, MD); University of Maryland School of Pharmacy, The PATIENTS Program (Baltimore, MD); PREP-IT Clinical Sites; Lead Clinical Site (Aqueous-PREP and PREPARE); University of Maryland School of Medicine, R Adams Cowley Shock Trauma Center, Baltimore, MD; Aqueous-PREP and PREPARE; Hamilton Health Sciences - General Site, Hamilton, ON; Prisma Health - Upstate, Greenville, SC; IU Health Methodist Hospital, Indianapolis, IN; San Antonio Military Medical Center, San Antonio, TX; University of California, San Francisco, San Francisco, CA; Aqueous-PREP; Vanderbilt Medical Center, Nashville, TN; University of Florida, Gainesville, FL; McGovern Medical School at UTHealth Houston, Houston, TX; Wright State University, Dayton, OH; Banner University Medical Center - Tucson, Tucson, AZ; CORE Institute, Phoenix, AZ; Vall d'Hebron University Hospital, Barcelona, Spain; Hospital Universitari Parc Tauli, Barcelona, Spain; PREPARE; FRASER HEALTH AUTHORITY/Royal Columbian Hospital, New Westminster, BC; Inova Fairfax Medical Campus, Falls Church, VA; Wake Forest Baptist Health, Winston-Salem, NC; MetroHealth Medical Center, Cleveland, OH; University of Utah, Salt Lake City, Utah; University of Mississippi Medical Center, Jackson, MS; Sanford Health, Sioux Falls, SD; Dartmouth-Hitchcock Medical Center, Lebanon, NH; Carolinas Medical Center, Atrium Health Musculoskeletal Institute, Charlotte, NC; University of Maryland, Capital Region Health, Largo, MD; University of Wisconsin Madison, Madison, WI; Duke University Hospital, Durham, NC; Brigham Women's Hospital, Boston, MA; University of Pennsylvania, Philadelphia, PA; Massachusetts General Hospital, Boston, MA; Bryan Medical Center, Lincoln, Nebraska; University of Cincinnati, Cincinnati, OH; Cedars-Sinai Medical Center, Los Angeles, CA; University of California, Irvine, Orange, CA. The impact of heterotopic ossification prophylaxis after surgical fixation of acetabular fractures: national treatment patterns and related outcomes. Injury. 2023 Jun;54(6):1693-1701. doi: 10.1016/j.injury.2023.03.001. Epub 2023 Mar 6.

    PubMed 37002119

  • 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.

    PubMed 32787892

  • 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.

    PubMed 32259266

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing DuraPrep and ChloraPrep in people with Surgical Site Infection and Unplanned Fracture-Related Reoperation, run by University of Maryland, Baltimore at 27 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Superficial Incisional Surgical Site Infection (SSI) (time frame: Within 30 days of the patient's last planned fracture management surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03523962, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2024.

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