Back to resultsPre-operative Aqueous Antiseptic Skin Solutions in Open Fractures (Aqueous-PREP)
Primary Purpose
Surgical Site Infection, Unplanned Fracture-Related Reoperation, Open Appendicular Fracture
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
10% povidone-iodine (1% free iodine) in purified water
4% chlorhexidine gluconate (CHG) in purified water
Sponsored by
About this trial
This is an interventional treatment trial for Surgical Site Infection focused on measuring Surgical Site Infection, Open Fracture, Povidone-iodine, Chlorhexidine gluconate, Peri-operative Preparation Solutions
Eligibility Criteria
The inclusion criteria are:
- 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.
The exclusion criteria are:
- 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.
Sites / Locations
- The CORE Institute / Banner University Medical Center
- Banner - University Medical Center Tucson
- University of California San Francisco
- University of Florida
- Indiana University Health Methodist Hospital
- University of Maryland, R Adams Cowley Shock Trauma Center
- Wright State University / Miami Valley Hospital
- Greenville Health System
- Vanderbilt University
- San Antonio Military Medical Center
- McGovern Medical School at University of Texas Health Science Center Houston
- Hamilton Health Sciences
- McMaster University, Center for Evidence-Based Orthopaedics
- Hospital Parc Tauli de Sabadell
- Vall d'Hebron University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
10% povidone-iodine (1% free iodine) in purified water
4% chlorhexidine gluconate (CHG) in purified water
Arm Description
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.).
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.).
Outcomes
Primary Outcome Measures
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:
purulent drainage from the superficial incision.
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
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.
diagnosis of a superficial incisional SSI by the surgeon.
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:
deep incision purulent drainage
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
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:
organ/space purulent drainage
organisms in organ/space identified by microbiologic testing
other evidence of organ/space infection on anatomical exam or imaging test
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT03385304
First Posted
December 20, 2017
Last Updated
March 6, 2023
Sponsor
University of Maryland, Baltimore
Collaborators
McMaster University, United States Department of Defense
1. Study Identification
Unique Protocol Identification Number
NCT03385304
Brief Title
Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures
Acronym
Aqueous-PREP
Official Title
Aqueous-PREP: A Pragmatic Randomized Trial Evaluating Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
April 8, 2018 (Actual)
Primary Completion Date
October 19, 2021 (Actual)
Study Completion Date
June 27, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
McMaster University, United States Department of Defense
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Site Infection, Unplanned Fracture-Related Reoperation, Open Appendicular Fracture
Keywords
Surgical Site Infection, Open Fracture, Povidone-iodine, Chlorhexidine gluconate, Peri-operative Preparation Solutions
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
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
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.
Allocation
Randomized
Enrollment
1638 (Actual)
8. Arms, Groups, and Interventions
Arm Title
10% povidone-iodine (1% free iodine) in purified water
Arm Type
Experimental
Arm Description
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.).
Arm Title
4% chlorhexidine gluconate (CHG) in purified water
Arm Type
Experimental
Arm Description
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.).
Intervention Type
Drug
Intervention Name(s)
10% povidone-iodine (1% free iodine) in purified water
Intervention Description
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
Intervention Name(s)
4% chlorhexidine gluconate (CHG) in purified water
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With a Superficial Incisional Surgical Site Infection (SSI)
Description
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:
purulent drainage from the superficial incision.
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
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.
diagnosis of a superficial incisional SSI by the surgeon.
Time Frame
Within 30 days of the patient's last planned fracture management surgery
Title
Number of Participants With a Deep Incisional or Organ/Space Infection
Description
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:
deep incision purulent drainage
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
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:
organ/space purulent drainage
organisms in organ/space identified by microbiologic testing
other evidence of organ/space infection on anatomical exam or imaging test
Time Frame
Within 90 days of the patient's last planned fracture management surgery
Secondary Outcome Measure Information:
Title
Number of Participants With an Unplanned Fracture-Related Reoperation
Description
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.
Time Frame
Within 12 months of the patient's last planned operation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
The inclusion criteria are:
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.
The exclusion criteria are:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard Slobogean, MD
Organizational Affiliation
University of Maryland Shock Trauma Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sheila Sprague, PhD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mohit Bhandari, MD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The CORE Institute / Banner University Medical Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Banner - University Medical Center Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85721
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
Indiana University Health Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Maryland, R Adams Cowley Shock Trauma Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Wright State University / Miami Valley Hospital
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Greenville Health System
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37240
Country
United States
Facility Name
San Antonio Military Medical Center
City
Fort Sam Houston
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
McGovern Medical School at University of Texas Health Science Center Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada
Facility Name
McMaster University, Center for Evidence-Based Orthopaedics
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 8E7
Country
Canada
Facility Name
Hospital Parc Tauli de Sabadell
City
Barcelona
Country
Spain
Facility Name
Vall d'Hebron University Hospital
City
Barcelona
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36096826
Citation
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.
Results Reference
background
PubMed Identifier
36244384
Citation
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. Erratum In: Lancet. 2023 Dec 17;400(10369):2198.
Results Reference
derived
PubMed Identifier
33648577
Citation
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.
Results Reference
derived
PubMed Identifier
32787892
Citation
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. Erratum In: Trials. 2020 Sep 30;21(1):821.
Results Reference
derived
PubMed Identifier
32259266
Citation
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.
Results Reference
derived
Learn more about this trial
Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures
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