Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures

NCT03385304 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: HP-00078470
• Study Type: interventional
• Target: 1,638
• Locations: 3 countries
• Sites: 15

Brief Summary

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.

Conditions

Surgical Site Infection; Unplanned Fracture-Related Reoperation; Open Appendicular Fracture

Keywords

Surgical Site Infection; Open Fracture; Povidone-iodine; Chlorhexidine gluconate; 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 or Organ/Space 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 Organ/Space Infection: Occurs within 90 days post definitive fracture management; \& involves any part of the body deeper than the fascial/muscle layers; \& has at least one of the following: 1. organ/space purulent drainage 2. organisms in organ/space identified by microbiologic testing 3. other evidence of organ/space 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)

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

EXPERIMENTAL

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.).

Drug: 10% povidone-iodine (1% free iodine) in purified water; Drug: 4% chlorhexidine gluconate (CHG) in purified water

4% chlorhexidine gluconate (CHG) in purified water

EXPERIMENTAL

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.).

Drug: 10% povidone-iodine (1% free iodine) in purified water; Drug: 4% chlorhexidine gluconate (CHG) in purified water

Interventions

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

10% povidone-iodine (1% free iodine) in purified water; 4% chlorhexidine gluconate (CHG) in purified water

4% chlorhexidine gluconate (CHG) in purified water 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.

10% povidone-iodine (1% free iodine) in purified water; 4% chlorhexidine gluconate (CHG) in purified water

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) (e.g., 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:

• Patients that 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 open fracture at a non-participating hospital or clinic.
• Open fracture managed outside of the participating orthopaedic service (e.g., hand fracture managed by plastic surgeon).
• 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.
• Previous enrollment in a PREP-IT trial.
• 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.
• Excluded due to sampling strategy.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• McMaster University: collaborator
• United States Department of Defense: collaborator

Study Sites (15)

The CORE Institute / Banner University Medical Center

Phoenix, Arizona, 85006, United States

Location

Banner - University Medical Center Tucson

Tucson, Arizona, 85721, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Indiana University Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Maryland, R Adams Cowley Shock Trauma Center

Baltimore, Maryland, 21201, United States

Location

Wright State University / Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Vanderbilt University

Nashville, Tennessee, 37240, United States

Location

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

McGovern Medical School at University of Texas Health Science Center Houston

Houston, Texas, 77030, United States

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

McMaster University, Center for Evidence-Based Orthopaedics

Hamilton, Ontario, L8L 8E7, Canada

Location

Hospital Parc Tauli de Sabadell

Barcelona, Spain

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

Related Publications (5)

• 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.

  PMID: 36096826 BACKGROUND

• 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.

  PMID: 36244384 DERIVED

• 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.

  PMID: 33648577 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; Fractures, Open

Interventions

Povidone-Iodine; chlorhexidine gluconate; Chromogranins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Iodophors; Iodine Compounds; Inorganic Chemicals; Polyvinyls; Vinyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Povidone; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Nerve Tissue Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors

Limitations and Caveats

The uncontrolled use of adjunctive skin preparations before final antisepsis is a potential limitation of our study design. Although the use of a prewash with adjunctive alcohol was similarly distributed between the treatment groups, post-randomization confounding from this practice might exist. The trial has other limitations, including unmasked treatment allocation and the decision to initiate each recruitment site as soon as possible.

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 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.
• 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 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: December 20, 2017
• First Posted: December 28, 2017
• Study Start: April 8, 2018
• Primary Completion: October 19, 2021
• Study Completion: June 27, 2022
• Last Updated: March 31, 2023
• Results First Posted: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (11); CA (2)