Prophylactic Antibiotic Coated Nail to Prevent Infection: A Clinical Trial

Tibial Fractures Clinical Trial

Official title:

Prophylactic Antibiotic Coated Nail to Prevent Infection: A Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05421741
• Other study ID #: IRB00086285
• Secondary ID: 01012022
• Status: Recruiting
• Phase: Phase 4
• Start date: May 15, 2023
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Wake Forest University Health Sciences
• Contact: Rachel Seymour, PhD
• Phone: 7043552000
• Email: Rachel.Seymour[@]atriumhealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective randomized clinical trial will compare outcomes between patients treated primarily with a prophylactic antibiotic coated nail and those treated with traditional standard of care intramedullary (IM) nailing.

Description:

Despite significant treatment advances and protocols to prevent infection, severe open fractures of the lower extremity still have very high rates of deep infection. Infection in an active duty military population increases disability and decreases the likelihood of returning to duty. In addition, infection is one of the main factors associated with rehospitalization. Further, deep infections have not only resulted in increased disability after injury, infection is implicated as one of the main factors in late amputation. Among service members, only 20-25% with a severe open tibia fracture are able to return to active duty. Novel techniques for reducing infection are needed. The proposed study addresses the focus area of fracture-related infections, specifically the prevention of infection. This prospective randomized clinical trial will compare outcomes between patients treated primarily with a prophylactic antibiotic coated nail and those treated with traditional standard of care intramedullary (IM) nailing. This prospective randomized clinical trial will compare outcomes between patients treated primarily with a prophylactic antibiotic coated nail and those treated with traditional standard of care intramedullary (IM) nailing. The target population for the proposed study is patients with severe open tibia fractures (Type II or Type III) who require definitive fixation with intramedullary nail recruited from one of the participating sites during the index hospitalization. One group will be treated prophylactically using an antibiotic coated intramedullary nail at time of definitive fixation (1CN), while the second group will be treated with traditional standard of care intramedullary nail without antibiotic-coating (SN). Participant will be followed for 12 months (data capture including patient interviews and clinical data capture from the treatment team and medical record at baseline, 6 weeks, 3 months, 6 months, and 12 months).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 484
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients 18 years or older
• Gustilo Type II or III open tibia fracture requiring definitive fixation with intramedullary nail

Exclusion Criteria:

• Less than 18 years of age
• Allergy to vancomycin or gentamicin
• Unable to speak English or Spanish
• Pregnant and lactating women
• Prisoner
• Unable to follow up for 12 months

Related Conditions & MeSH terms

• Fractures, Bone
• Open Tibia Fracture
• Osteomyelitis
• Osteomyelitis Tibia
• Tibial Fractures

Intervention

Drug:
• Antibiotic coated intramedullary Nail
Antibiotic coated intramedullary nail: A mixture of 40gm bag of acrylic cement, antibiotic powder (Vancomycin 2gm) and 560mg gentamicin liquid. The intramedullary is coated with the mixture using a cement gun tube.

Other:
• Standard Intramedullary Nail
Standard Intramedullary Nail

Locations

Country	Name	City	State
United States	University of North Carolina Chapel Hill	Chapel Hill	North Carolina
United States	Atrium Health Carolinas Medical Center	Charlotte	North Carolina
United States	Atrium Health Cabarrus	Concord	North Carolina
United States	Inova	Fairfax	Virginia
United States	University of Florida Gainesville	Gainesville	Florida
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Texas Houston	Houston	Texas
United States	University of Kentucky	Lexington	Kentucky
United States	Atrium Health Navicent	Macon	Georgia
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Louisiana State University - University Medical Center New Orleans	New Orleans	Louisiana
United States	San Antonio Military Medical Center	San Antonio	Texas
United States	Florida Orthopaedic Institute	Temple Terrace	Florida
United States	Valley Health System	Winchester	Virginia
United States	Atrium Health Wake Forest Baptist	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (38)

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Bratzler DW, Houck PM; Surgical Infection Prevention Guidelines Writers Workgroup; American Academy of Orthopaedic Surgeons; American Association of Critical Care Nurses; American Association of Nurse Anesthetists; American College of Surgeons; American C — View Citation

Burns TC, Stinner DJ, Mack AW, Potter BK, Beer R, Eckel TT, Possley DR, Beltran MJ, Hayda RA, Andersen RC, Keeling JJ, Frisch HM, Murray CK, Wenke JC, Ficke JR, Hsu JR; Skeletal Trauma Research Consortium. Microbiology and injury characteristics in severe — View Citation

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Carver DC, Kuehn SB, Weinlein JC. Role of Systemic and Local Antibiotics in the Treatment of Open Fractures. Orthop Clin North Am. 2017 Apr;48(2):137-153. doi: 10.1016/j.ocl.2016.12.005. Epub 2017 Jan 30. — View Citation

Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, Choi S, Cook K, Devellis R, DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P, Revicki D, Rose M, Weinfurt K, Hays R; PROMIS Cooperative Group. The Patient-Repo — View Citation

Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, Ader D, Fries JF, Bruce B, Rose M; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two — View Citation

Centers for Disease Control and Prevention. Surgical Site Infection (SSI) Event, January 2018. National Healthcare Safety Network. 2018

Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10. — View Citation

Cross JD, Stinner DJ, Burns TC, Wenke JC, Hsu JR; Skeletal Trauma Research Consortium (STReC). Return to duty after type III open tibia fracture. J Orthop Trauma. 2012 Jan;26(1):43-7. doi: 10.1097/BOT.0b013e31821c0ec1. — View Citation

Dreyer NA, Tunis SR, Berger M, Ollendorf D, Mattox P, Gliklich R. Why observational studies should be among the tools used in comparative effectiveness research. Health Aff (Millwood). 2010 Oct;29(10):1818-25. doi: 10.1377/hlthaff.2010.0666. — View Citation

Ficke JR, Pollak AN. Extremity War Injuries: Development of Clinical Treatment Principles. J Am Acad Orthop Surg. 2007 Oct;15(10):590-5. doi: 10.5435/00124635-200710000-00003. — View Citation

Hanssen AD, Osmon DR, Patel R. Local antibiotic delivery systems: where are we and where are we going? Clin Orthop Relat Res. 2005 Aug;(437):111-4. No abstract available. — View Citation

Huh J, Stinner DJ, Burns TC, Hsu JR; Late Amputation Study Team. Infectious complications and soft tissue injury contribute to late amputation after severe lower extremity trauma. J Trauma. 2011 Jul;71(1 Suppl):S47-51. doi: 10.1097/TA.0b013e318221181d. — View Citation

Johnson EN, Burns TC, Hayda RA, Hospenthal DR, Murray CK. Infectious complications of open type III tibial fractures among combat casualties. Clin Infect Dis. 2007 Aug 15;45(4):409-15. doi: 10.1086/520029. Epub 2007 Jul 5. — View Citation

Jorge-Mora A, Amhaz-Escanlar S, Fernandez-Pose S, Garcia-Iglesias A, Mandia-Mancebo F, Franco-Trepat E, Guillan-Fresco M, Pino-Minguez J. Commercially available antibiotic-laden PMMA-covered locking nails for the treatment of fracture-related infections - — View Citation

Kooistra BW, Dijkman BG, Busse JW, Sprague S, Schemitsch EH, Bhandari M. The radiographic union scale in tibial fractures: reliability and validity. J Orthop Trauma. 2010 Mar;24 Suppl 1:S81-6. doi: 10.1097/BOT.0b013e3181ca3fd1. — View Citation

Lin WT, Tan HL, Duan ZL, Yue B, Ma R, He G, Tang TT. Inhibited bacterial biofilm formation and improved osteogenic activity on gentamicin-loaded titania nanotubes with various diameters. Int J Nanomedicine. 2014 Mar 7;9:1215-30. doi: 10.2147/IJN.S57875. e — View Citation

Masini BD, Owens BD, Hsu JR, Wenke JC. Rehospitalization after combat injury. J Trauma. 2011 Jul;71(1 Suppl):S98-102. doi: 10.1097/TA.0b013e3182218fbc. — View Citation

Mauffrey C, Butler N, Hake ME. Fabrication of an Interlocked Antibiotic/Cement-Coated Carbon Fiber Nail for the Treatment of Long Bone Osteomyelitis. J Orthop Trauma. 2016 Aug;30 Suppl 2:S23-4. doi: 10.1097/BOT.0000000000000587. — View Citation

Napierala MA, Rivera JC, Burns TC, Murray CK, Wenke JC, Hsu JR; Skeletal Trauma Research Education Consortium (STReC). Infection reduces return-to-duty rates for soldiers with Type III open tibia fractures. J Trauma Acute Care Surg. 2014 Sep;77(3 Suppl 2) — View Citation

O'Toole R, Joshi M, Carlini A, et al. Multicenter Randomized Trial Evaluating Intrawound Vancomycin Powder for Reducing Surgical Site Infection After Fracture Surgery. Orthopaedic Trauma Association; 2018; Orlando, FL

O'Toole RV, Joshi M, Carlini AR, Murray CK, Allen LE, Scharfstein DO, Gary JL, Bosse MJ, Castillo RC; METRC. Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection: A Multicenter, Randomized, Controll — View Citation

Owens BD, Kragh JF Jr, Macaitis J, Svoboda SJ, Wenke JC. Characterization of extremity wounds in Operation Iraqi Freedom and Operation Enduring Freedom. J Orthop Trauma. 2007 Apr;21(4):254-7. doi: 10.1097/BOT.0b013e31802f78fb. — View Citation

Pinto D, Manjunatha K, Savur AD, Ahmed NR, Mallya S, Ramya V. Comparative study of the efficacy of gentamicin-coated intramedullary interlocking nail versus regular intramedullary interlocking nail in Gustilo type I and II open tibia fractures. Chin J Tra — View Citation

Schalet BD, Rothrock NE, Hays RD, Kazis LE, Cook KF, Rutsohn JP, Cella D. Linking Physical and Mental Health Summary Scores from the Veterans RAND 12-Item Health Survey (VR-12) to the PROMIS((R)) Global Health Scale. J Gen Intern Med. 2015 Oct;30(10):1524 — View Citation

Schmidmaier G, Kerstan M, Schwabe P, Sudkamp N, Raschke M. Clinical experiences in the use of a gentamicin-coated titanium nail in tibia fractures. Injury. 2017 Oct;48(10):2235-2241. doi: 10.1016/j.injury.2017.07.008. Epub 2017 Jul 10. — View Citation

Section 1: Preventing and Managing Infection and Other Complications After Orthopaedic Trauma. J Orthop Trauma. 2017 Apr;31 Suppl 1:S2. doi: 10.1097/BOT.0000000000000798. No abstract available. — View Citation

Selim AJ, Rogers W, Fleishman JA, Qian SX, Fincke BG, Rothendler JA, Kazis LE. Updated U.S. population standard for the Veterans RAND 12-item Health Survey (VR-12). Qual Life Res. 2009 Feb;18(1):43-52. doi: 10.1007/s11136-008-9418-2. Epub 2008 Dec 3. — View Citation

Shiels SM, Mangum LH, Wenke JC. Revisiting the "race for the surface" in a pre-clinical model of implant infection. Eur Cell Mater. 2020 Jan 29;39:77-95. doi: 10.22203/eCM.v039a05. — View Citation

Shiels SM, Tennent DJ, Lofgren AL, Wenke JC. Topical rifampin powder for orthopaedic trauma part II: Topical rifampin allows for spontaneous bone healing in sterile and contaminated wounds. J Orthop Res. 2018 Dec;36(12):3142-3150. doi: 10.1002/jor.24155. — View Citation

Shiels SM, Tennent DJ, Wenke JC. Topical rifampin powder for orthopedic trauma part I: Rifampin powder reduces recalcitrant infection in a delayed treatment musculoskeletal trauma model. J Orthop Res. 2018 Dec;36(12):3136-3141. doi: 10.1002/jor.24055. Epu — View Citation

Tennent DJ, Shiels SM, Sanchez CJ Jr, Niece KL, Akers KS, Stinner DJ, Wenke JC. Time-Dependent Effectiveness of Locally Applied Vancomycin Powder in a Contaminated Traumatic Orthopaedic Wound Model. J Orthop Trauma. 2016 Oct;30(10):531-7. doi: 10.1097/BOT — View Citation

Thonse R, Conway J. Antibiotic cement-coated interlocking nail for the treatment of infected nonunions and segmental bone defects. J Orthop Trauma. 2007 Apr;21(4):258-68. doi: 10.1097/BOT.0b013e31803ea9e6. — View Citation

Whelan DB, Bhandari M, Stephen D, Kreder H, McKee MD, Zdero R, Schemitsch EH. Development of the radiographic union score for tibial fractures for the assessment of tibial fracture healing after intramedullary fixation. J Trauma. 2010 Mar;68(3):629-32. do — View Citation

* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants who develop deep surgical site infection (SSI)	Number of participants in each group who develop SSI as defined by the criteria establish by the Centers for Disease Control and Prevention (CDC). The CDC criteria define deep as occurring within 30 or 90 days after the procedure. However, we will continue to follow patients for 12 months and document any infections and other complications during this period.	Day 30 through month 12
Secondary	Radiographic Union Scale in Tibial fractures (RUST) score	The RUST score ranges from a minimum score of 4 (definitely not healed) to a maximum score of 12 (completely healed). The final x-ray obtained within a 12-month period following injury will be uploaded to REDCap for review by a blinded panel of investigators from participating sites.	week 6, month 3, month 6, and month 12
Secondary	Percentage of Union	Union is the gradual process of bone regeneration after a fracture. Percentage of Union, as determined by the treating surgeon, will be assessed via radiographs. Recorded by surgeon as yes/no answers.	week 6, month 3, month 6 and month12
Secondary	Time to Union	Captured in days	week 6, month 3, month 6 and month12
Secondary	Average Time to Return to Work/Duty	number of days	week 6, month 3, month 6 and month12
Secondary	International Physical Activity Questionnaire (IPAQ)	IPAQ measures the total amount of physical activity completed in a 7 day period by calculating the minutes per week in in each physical activity level domain (walking, moderate and vigorous) by a metabolic equivalent energy (MET) expenditure estimate.; Walking = 3.3 x number of walking minutes x number of walking days Moderate activity= 4.0 x number activity minutes x number of days Vigorous activity = 8 x number of activity minutes x number of days Total = Walking MET-min/wk+moderate MET-min/wk+vigorous MET-min/wk	week 6, month 3, month 6 and month12
Secondary	Number of Subjects Who Have Returned to Work	Determined by asking whether subjects have returned to work	week 6, month 3, month 6 and month12
Secondary	Number of Participants who Return to Operating Room (OR)		Month 12
Secondary	PROMIS-29 Subscale--Physical Function	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means higher physical function.	week 6, month 3, month 6 and month12
Secondary	PROMIS-29 Subscale--Physical Function: Anxiety	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of anxiety.	week 6, month 3, month 6 and month12
Secondary	PROMIS-29 Subscale--Depression	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of depression.	week 6, month 3, month 6 and month12
Secondary	PROMIS-29 Subscale--Fatigue	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of fatigue.	week 6, month 3, month 6 and month12
Secondary	PROMIS-29 Subscale--Sleep Disturbance	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of sleep disturbance.	week 6, month 3, month 6 and month12
Secondary	PROMIS-29 Subscale--Pain Interference	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher level of pain interference.	week 6, month 3, month 6 and month12
Secondary	PROMIS-29 Subscale--Ability to Participate in Social Roles and Activities	The PROMIS-29 scales will be scored using a T-score metric method. A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Higher scores means a higher ability to participate in social roles and activities.	week 6, month 3, month 6 and month12