Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures (Aqueous-PREP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03385304
Recruitment Status : Completed
First Posted : December 28, 2017
Results First Posted : March 31, 2023
Last Update Posted : March 31, 2023
Sponsor:
Collaborators:
McMaster University
United States Department of Defense
Information provided by (Responsible Party):
Gerard Slobogean, University of Maryland, Baltimore

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Surgical Site Infection Unplanned Fracture-Related Reoperation Open Appendicular Fracture Drug: 10% povidone-iodine (1% free iodine) in purified water Drug: 4% chlorhexidine gluconate (CHG) in purified water Phase 4

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1638 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Aqueous-PREP: A Pragmatic Randomized Trial Evaluating Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures
Actual Study Start Date : April 8, 2018
Actual Primary Completion Date : October 19, 2021
Actual Study Completion Date : June 27, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fractures

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: 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.).
 Drug: 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.

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.
Experimental: 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.).
 Drug: 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.

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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 ]

    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.

  2. Number of Participants With a Deep Incisional or Organ/Space Infection [ Time Frame: Within 90 days of the patient's last planned fracture management surgery ]

    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


Secondary Outcome Measures :
  1. Number of Participants With an Unplanned Fracture-Related Reoperation [ Time Frame: Within 12 months of the patient's last planned operation ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

The 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) (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.

The exclusion criteria are:

  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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03385304


Locations
Layout table for location information
United States, Arizona
The CORE Institute / Banner University Medical Center
Phoenix, Arizona, United States, 85006
Banner - University Medical Center Tucson
Tucson, Arizona, United States, 85721
United States, California
University of California San Francisco
San Francisco, California, United States, 94143
United States, Florida
University of Florida
Gainesville, Florida, United States, 32611
United States, Indiana
Indiana University Health Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Maryland
University of Maryland, R Adams Cowley Shock Trauma Center
Baltimore, Maryland, United States, 21201
United States, Ohio
Wright State University / Miami Valley Hospital
Dayton, Ohio, United States, 45409
United States, South Carolina
Greenville Health System
Greenville, South Carolina, United States, 29605
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37240
United States, Texas
San Antonio Military Medical Center
Fort Sam Houston, Texas, United States, 78234
McGovern Medical School at University of Texas Health Science Center Houston
Houston, Texas, United States, 77030
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada, L8L 2X2
McMaster University, Center for Evidence-Based Orthopaedics
Hamilton, Ontario, Canada, L8L 8E7
Spain
Hospital Parc Tauli de Sabadell
Barcelona, Spain
Vall d'Hebron University Hospital
Barcelona, Spain
Sponsors and Collaborators
University of Maryland, Baltimore
McMaster University
United States Department of Defense
Investigators
Layout table for investigator information
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
  Study Documents (Full-Text)

Documents provided by Gerard Slobogean, University of Maryland, Baltimore:
Study Protocol and Statistical Analysis Plan  [PDF] November 4, 2019

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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.

Layout table for additonal information
Responsible Party: Gerard Slobogean, Assistant Professor, Department of Orthopaedics, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT03385304    
Other Study ID Numbers: HP-00078470
First Posted: December 28, 2017    Key Record Dates
Results First Posted: March 31, 2023
Last Update Posted: March 31, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by Gerard Slobogean, University of Maryland, Baltimore:
Surgical Site Infection
Open Fracture
Povidone-iodine
Chlorhexidine gluconate
Peri-operative Preparation Solutions
Additional relevant MeSH terms:
Layout table for MeSH terms
Surgical Wound Infection
Fractures, Bone
Fractures, Open
Infections
Wounds and Injuries
Wound Infection
Postoperative Complications
Pathologic Processes
Iodine
Chlorhexidine
Chlorhexidine gluconate
 Povidone-Iodine
Povidone
Anti-Infective Agents, Local
Anti-Infective Agents
Disinfectants
Dermatologic Agents
Trace Elements
Micronutrients
Physiological Effects of Drugs
Plasma Substitutes
Blood Substitutes