Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures

NCT ID: NCT03385304

Last Updated: 2023-03-31

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

1638 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-08

Study Completion Date

2022-06-27

Brief Summary

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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.

Detailed Description

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Conditions

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Surgical Site Infection Unplanned Fracture-Related Reoperation Open Appendicular Fracture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
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.

Study Groups

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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.).

Group Type EXPERIMENTAL

10% povidone-iodine (1% free iodine) in purified water

Intervention Type DRUG

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

Intervention Type DRUG

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.

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.).

Group Type EXPERIMENTAL

10% povidone-iodine (1% free iodine) in purified water

Intervention Type DRUG

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

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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.

Exclusion Criteria

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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McMaster University

OTHER

Sponsor Role collaborator

United States Department of Defense

FED

Sponsor Role collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role lead

Responsible Party

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Gerard Slobogean

Assistant Professor, Department of Orthopaedics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gerard Slobogean, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Sheila Sprague, PhD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Mohit Bhandari, MD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

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The CORE Institute / Banner University Medical Center

Phoenix, Arizona, United States

Site Status

Banner - University Medical Center Tucson

Tucson, Arizona, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Indiana University Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status

University of Maryland, R Adams Cowley Shock Trauma Center

Baltimore, Maryland, United States

Site Status

Wright State University / Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Greenville Health System

Greenville, South Carolina, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Site Status

McGovern Medical School at University of Texas Health Science Center Houston

Houston, Texas, United States

Site Status

Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

McMaster University, Center for Evidence-Based Orthopaedics

Hamilton, Ontario, Canada

Site Status

Hospital Parc Tauli de Sabadell

Barcelona, , Spain

Site Status

Vall d'Hebron University Hospital

Barcelona, , Spain

Site Status

Countries

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United States Canada Spain

References

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O'Hara NN, Heels-Ansdell D, Bzovsky S, Dodds S, Thabane L, Bhandari M, Guyatt G, Devereaux PJ, Slobogean GP, Sprague S; PREP-IT Investigators. A pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): statistical analysis plan. Trials. 2022 Sep 12;23(1):772. doi: 10.1186/s13063-022-06541-0.

Reference Type BACKGROUND
PMID: 36096826 (View on PubMed)

PREP-IT Investigators. Aqueous skin antisepsis before surgical fixation of open fractures (Aqueous-PREP): a multiple-period, cluster-randomised, crossover trial. Lancet. 2022 Oct 15;400(10360):1334-1344. doi: 10.1016/S0140-6736(22)01652-X.

Reference Type DERIVED
PMID: 36244384 (View on PubMed)

Sprague S, Guyatt P, Bzovsky S, Nguyen U, Bhandari M, Thabane L, Petrisor B, Johal HS, Leonard J, Dodds S, Mossuto F, O'Toole RV, Howe A, Demyanovich HK, Camara M, O'Hara NN, Slobogean GP; PREP-IT Investigators. Pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solution in open fractures (Aqueous-PREP): the feasibility of a cluster randomized crossover study. Pilot Feasibility Stud. 2021 Mar 1;7(1):61. doi: 10.1186/s40814-021-00800-8.

Reference Type DERIVED
PMID: 33648577 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32787892 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32259266 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HP-00078470

Identifier Type: -

Identifier Source: org_study_id

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