Clinical trial NCT05402995
Conditions: Gustilo-Anderson Type III Open Tibia Fracture
Sponsor: Brett D. Crist
Start date: 2022-06-21; Completion date: 2023-08-31
Enrollment: 6 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Early debridement and definitive fixation, at the initial operative setting, historically led to no difference in the infection rates for Gustilo-Anderson type III open tibia fractures. However, Lenarz et al. reported that delaying definitive fixation in open tibia fractures could decrease the deep infection rate. At the University of Missouri, the investigators found that staged procedures, including initial debridement-temporary fixation and delayed definitive fixation, did not statistically decrease the rate of deep infection in Gustilo-Anderson type III fractures, prompting the study that is being proposed here. Antibiotic cement coated intramedullary nails have been used in management of infected long bone fractures. Since external fixation and staged debridement did not decrease type III open tibia infection rate, the investigators wanted to consider using antibiotic cement coated nails to deliver antibiotics locally in the acute open fracture setting to prophylactically decrease associated infection rate. Additionally, Irrisept is a wound irrigant that has been used to lower infection rates in different wound settings. To the investigators' knowledge, there are no robust data showing its effectiveness at lowering infection rates in open tibia fracture management. The purpose of this study is to determine the effects of Irrisept and antibiotic nails on lowering deep infection rates in type III open tibia fractures.

Detailed description:

Arms: arm 1: This is the standard of care management. Patient will go to the operating room (OR) first for irrigation and debridement with normal saline and external fixation. Will return to OR at a later date for definitive fixation. arm 2: Patient will go to the operating room (OR) first for irrigation and debridement with Irrisept (the experimental irrigation solution) and external fixation. Will return to OR at a later date for definitive fixation. arm 3: Patient will go to the operating room (OR) for treatment with an antibiotic-coated nail and have irrigation and debridement with normal saline. arm 4: Patient will go to the operating room (OR) for treatment with an antibiotic-coated nail and have irrigation and debridement with Irrisept (the experimental irrigation solution).
Interventions: intervention 1: Irrisept (Irrigation Solution) intervention 2: Saline
Intervention descriptions: intervention 1: Irrisept Antimicrobial Wound Lavage is intended for mechanical cleansing and removal of debris, dirt and foreign materials, including microorganisms from wounds. intervention 2: Saline irrigation

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 5 
BIOMEDICAL RESEARCH PROTOCOL  
UNIVERSITY OF MISSOURI 
 
Project Title: Prospective Randomized Control Trial Comparing Irrisept to Saline Irrigation for 
the Prevention of Infection After Open Tibia Fractures 
IRB Number: 2086908 
Version Number: 4 
Version Date: 04/04/2023 
Principal Investigator: Brett Crist, MD 
Funding Source: Investigator-initiated Grant: Irrimax 
 
 
 
 
 
1. Background 
 
Open tibia fractures are at high risk for deep infection (Tornetta et al.). Irrisept is a wound 
irrigant that has been used to lower infection rates in different wound settings.6,7 To the 
investigators’ knowledge, there are no robust data showing its effectiveness at lowering 
infection rates in open tibia fracture management.  Therefore, the primary purpose of this study 
is to determine the effects of Irrisept versus normal saline on deep infection rate following 
treatment of open tibial fractures.  Secondarily, we will perform subcohort analyses to assess 
the effects of severity grade (type I vs II vs II open) on deep infection rates in open tibia 
fractures. 
2. Research Objectives 
a. Primary 
i. 90-day surgical site infection (SSI) incidence 
b. Secondary 
i. Fracture healing at 6 months 
ii. PROMIS and VAS patient reported outcomes 
 
 
 
1. This study is designed to prospectively compare post-operative infection rates in patients 
treated for open tibia fractures and wounds irrigated with one of two solutions.  
2. Patients will be randomized to one of the two treatments: 
i. Normal Saline 
ii. Irrisept 
3. Patients with open tibia fractures will undergo standard operative debridement and 
appropriate fixation based on the severity and contamination of the fracture. 
4. Normal saline is a mix of sodium chloride and sterile water.  It has a number of uses in 
medicine including cleaning wounds. 
I. 
Research Objectives/Background 
II. 
Drugs/Biologics 


Page 2 of 5 
5. Irrisept is a wound debridement and cleansing lavage system. It contains low 
concentrations of Chlorhexidine Gluconate (CHG) 0.05% in sterile water. One bottle 
contains 450 mL 0.05% CHG in sterile water, USP 99.95%. Irrisept is cleared as a Class 
II Medical Device and an unclassified Combination Product. It can be used as SOC to 
washout open tibia fractures. 
 
 
 
1. Recruitment will take place in a private space in the University of Missouri Health 
System, after identifying a patient over the age of 18 who has an open tibial fracture. 
2. Potential participants will be pre-screened initially via medical record/PowerChart/they 
will then be screened in person to ensure all entry criteria are met.  
 
 
 
1. Consent will be obtained from the potential study subject him or herself. Properly trained 
and authorized personnel from the research staff or the treatment team will present the 
study to the potential subject, give them the informed consent to read, review the consent 
document with the subject and allow them time to consider participation and ask 
questions. The potential subject will sign and date the informed consent prior to any 
research activity.  
 
 
 
1. Inclusion 
a. Adult, 18 or over 
b. Open tibia fracture 
c. Able to obtain informed consent from patient  
2. Exclusion 
a. Minor, under 18 
b. Pregnancy 
c. Prisoner  
d. Allergic to chlorhexidine gluconate 
e. Unable to provide informed consent  
 
 
 
 
1. We plan to enroll 230 participants (n=230 subjects) (100 subjects per group, 30 screen 
fails) for a 2-year study. This will allow complete data for at least 200 who will complete 
the one-year follow-up.  
2. This sample size was determined by a pre-study power analysis based on 10% reduction 
in 90-day SSI incidence with a desired power of 0.8 and alpha set at <0.05. 
 
 
 
III. 
Recruitment Process 
IV. 
Consent Process 
V. 
Inclusion/Exclusion Criteria 
VI. 
Number of Subjects 
VII. 
Study Procedures/ Design/Treatment Plan 


Page 3 of 5 
 
1. Randomization Process 
a. After informed consent is obtained, all patients who meet eligibility 
criteria will be randomized into one of two groups. Randomization will be 
achieved by numbering 230 sealed envelopes (115 Irrisept, 115 Normal 
Saline). There is no blinding to the randomization. It would be difficult to 
blind the participants or research personnel. 
b. Standard of care at this institution is irrigation with normal saline and 
debridement.  
c. If randomized to the Irrisept group, patients will be removed from 
standard of care. 
2. Surgery 
a. Patients will be screened and randomized prior to going to the operating 
room for the initial operative debridement of the open tibia fracture. They 
will return to the operating room for as many operative debridements as 
necessary until the definitive fixation surgery is performed.  
b. One group will utilize only Irrisept solution for all open fracture 
debridements and irrigations, and the other will utilize only normal saline 
for all debridements and irrigations. Surgical sites that are not the open 
fracture site should be irrigated with normal saline as per standard of care. 
c. The subjects will undergo standard operative debridement and fixation. 
d. All other components of the management will be standard—antibiotics 
pre- and postop, surgical debridement, dressings/use of negative pressure 
wound therapy, etc. 
3. Clinical Follow-Up 
a. Standard of Care Standard of Care (SOC)—2 weeks, 6 weeks, 3 months, 6 
months and 1 year with tibia radiographs at each visit except the 2-week 
follow up.  Study window will be +/- 2 weeks starting at the 6-week visit. 
b. Tibia radiographs will be collected at each visit per SOC to assess fracture 
healing as 0-not healed; 1-partially healed; or 2-completely healed. 
c. Deep infection rate as well as wound healing will be assessed. Developing 
infection would be monitored regardless of the subject’s participation in 
the study.  
d. Patient reported outcomes including PROMIS and VAS pain scores will 
be collected at each visit per SOC.  
e. Subjects will be monitored at follow-ups for unanticipated events.  
4. Subjects will be removed if they do not return to their follow-up visits or do not complete 
the study specific tasks.  
5. Subjects that are removed prematurely or complete the study will continue routine care 
per physician’s standard of care treatment.  
6. No specimens will be collected for research purposes. 
7. Statistical Analysis – significance set at p<0.05. 
a. Primary Outcome Measure: CDC-defined 90-day surgical site infection 
(SSI) incidence – compared among groups using chi-square test.  
b. Secondary Outcome Measure: Fracture healing at 6 months post-op – 
compared between groups using a rank sum test. 


Page 4 of 5 
c. Secondary Outcome Measures: PROMIS and VAS Pain scores – 
compared between groups using unpaired t-Tests. 
d. Secondary Outcome Measure: Multivariate analyses will be used to assess 
the effects of severity grade (type I vs II vs II open)on deep infection rates 
in open tibia fractures.  
 
 
1. Risks 
a. Risks for breach of confidentiality does exist but will be limited with tight control 
of data and limited access to the investigators/study team. 
b. There is a minimal increased risk of reaction to chlorhexidine gluconate in the 
Irrisept treatment group which may include allergic reaction or irritation.   
2. Any complications arising from the use of the Irrisept irrigation will be reported to the 
IRB within 5 days.  
 
 
 
 
1. There is no guarantee of direct benefit to study participants. 
a. The data collected will contribute to the orthopaedic knowledge base. We hope it 
can be implemented to provide improved evidence-based care of these injuries. 
b. Potential benefits include possible lower risk of infection and decreased overall 
healthcare costs. 
 
 
 
 
1. No compensation will be provided to the subjects.  
 
 
 
 
1. No research specific costs will be incurred by the research subjects. 
2. Standard of care procedures will be billed to the insurance/third party payor/participant. 
The costs associated with this study are outlined below: 
1. Cost of research support (IRB submission and maintenance, storage and management of study 
documents, statistical support) = $50,000 
2. IRB Fees = $5,500.00 ($2,500 Initial Approval + $1,500.00 Annual Review) 
3. Cost of product ($65 x 200 in experimental group) = $ 13,000– Budgeting for 2 bottles of 
Irrisept solution per case. 
 
 
 
1. Patient confidentiality during the course of this study will be protected in compliance 
with HIPAA requirements as well as the requirements of the University of Missouri 
Health-Sciences IRB.  
VIII. Potential Risks/Adverse Events 
IX. 
Anticipated Benefits 
X. 
Compensation 
XII. 
Data Safety Monitoring Plan 
XI. 
Costs 


Page 5 of 5 
2. All subjects will be assigned a study identification number that requires the use of a key 
in order to decipher a subject’s personal identification information. The key will be kept 
in a secure electronic location, which is password protected. The study identification 
number will be used to label all paper data collection instruments.  
3. All subject information in electronic format will be kept in password-protected storage. 
All subject information in paper format will be kept in locked cabinets in a secured suite 
at the Missouri Orthopedic Institute, and otherwise will be archived in a secure storage 
facility or destroyed.  
4. Data will be stored on the Department of Orthopaedic Surgery shared drive and/or 
PatientIQ, a HIPAA-compliant cloud-based platform that is contracted with the 
department of orthopaedic surgery.  
 
 
 
1.  Court-Brown CM, McQueen MM, Quaba AA, Christie J. Locked intramedullary nailing of 
open tibial fractures. J Bone Joint Surg Br. 1991;73(6):959-964. doi:10.1302/0301-
620X.73B6.1955445 
2.  Tornetta P, Bergman M, Watnik N, Berkowitz G, Steuer J. Treatment of grade-IIIb open 
tibial fractures. A prospective randomised comparison of external fixation and non-reamed 
locked nailing. J Bone Joint Surg Br. 1994;76(1):13-19. 
3.  Lenarz CJ, Watson JT, Moed BR, Israel H, Mullen JD, Macdonald JB. Timing of wound 
closure in open fractures based on cultures obtained after debridement. J Bone Joint Surg 
Am. 2010;92(10):1921-1926. doi:10.2106/JBJS.I.00547 
4.  Meinberg EG, Agel J, Roberts CS, Karam MD, Kellam JF. Fracture and Dislocation 
Classification Compendium-2018. J Orthop Trauma. 2018;32 Suppl 1:S1-S170. 
doi:10.1097/BOT.0000000000001063 
5.  Liu JZ, Crist BD. Coated nails: is their use supported by the literature? OTA International. 
2021;4(3S):e110. doi:10.1097/OI9.0000000000000110 
6.  Arslan NC, Degirmenci AK, Ozdenkaya Y, Terzi C. Wound Irrigation with Chlorhexidine 
Gluconate Reduces Surgical Site Infection in Pilonidal Disease: Single-Blind Prospective 
Study. Surg Infect (Larchmt). 2020;21(2):143-149. doi:10.1089/sur.2019.053 
7.  Goztok M, Terzi MC, Egeli T, Arslan NC, Canda AE. Does Wound Irrigation with 
Clorhexidine Gluconate Reduce the Surgical Site Infection Rate in Closure of Temporary 
Loop Ileostomy? A Prospective Clinical Study. Surg Infect (Larchmt). 2018;19(6):634-639. 
doi:10.1089/sur.2018.061 
 
XIV. References/Appendices