Aqueous-PREP: Pre-operative Aqueous Antiseptic Skin Solutions in Open Fractures

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Completed

CT.gov ID

NCT03385304

Collaborator

McMaster University (Other), United States Department of Defense (U.S. Fed)

1,683

Enrollment

Locations

Arms

50.8

Actual Duration (Months)

112.2

Patients Per Site

2.2

Patients Per Site Per Month

Study Details

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.

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

Study Type:

Interventional

Actual Enrollment :

1683 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.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 :

Apr 3, 2018

Actual Primary Completion Date :

Oct 19, 2021

Actual Study Completion Date :

Jun 27, 2022

Arms and Interventions

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.

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

Outcome Measures

Primary Outcome Measures

Surgical Site Infection: Superficial Incisional [Within 30 days of the patient's last planned fracture management surgery]
Guided by the CDC's National Healthcare Safety Network reporting criteria
Surgical Site Infection: Deep Incisional or Organ/Space [Within 90 days of the patient's last planned fracture management surgery]
Guided by the CDC's National Healthcare Safety Network reporting criteria

Secondary Outcome Measures

Unplanned Fracture-Related Reoperation [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The CORE Institute / Banner University Medical Center	Phoenix	Arizona	United States	85006
2	Banner - University Medical Center Tucson	Tucson	Arizona	United States	85721
3	University of California San Francisco	San Francisco	California	United States	94143
4	University of Florida	Gainesville	Florida	United States	32611
5	Indiana University Health Methodist Hospital	Indianapolis	Indiana	United States	46202
6	University of Maryland, R Adams Cowley Shock Trauma Center	Baltimore	Maryland	United States	21201
7	Wright State University / Miami Valley Hospital	Dayton	Ohio	United States	45409
8	Greenville Health System	Greenville	South Carolina	United States	29605
9	Vanderbilt University	Nashville	Tennessee	United States	37240
10	San Antonio Military Medical Center	Fort Sam Houston	Texas	United States	78234
11	McGovern Medical School at University of Texas Health Science Center Houston	Houston	Texas	United States	77030
12	Hamilton Health Sciences	Hamilton	Ontario	Canada	L8L 2X2
13	McMaster University, Center for Evidence-Based Orthopaedics	Hamilton	Ontario	Canada	L8L 8E7
14	Hospital Parc Tauli de Sabadell	Barcelona		Spain
15	Vall d'Hebron University Hospital	Barcelona		Spain

Sponsors and Collaborators

University of Maryland, Baltimore
McMaster University
United States Department of Defense

Investigators

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