Clinical trial NCT06640491: Intraosseous (IO) Cefazolin and Vancomycin in Primary Total Knee Arthroplasty (TKA)
Official title: Intraosseous Vancomycin and Cefazolin vs Intravenous Administration in Primary Total Knee Arthroplasty
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Total Knee Arthroplasty
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
First posted: 2024-10-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the efficacy of intravenous (IV) and intraosseous (IO) antibiotic administration techniques during primary total knee arthroplasty (TKA) in adults undergoing a TKA procedure at Houston Methodist Hospital. The main questions it aims to answer are:

Does IO administration of vancomycin and cefazolin protect against perioperative exposure risks? Is there a difference in post-operative complication rates between IV and IO administration of these drugs?

Participants will be randomized to receive either the standard of care IV administration of Vancomycin and Cefazolin, or the IO administration of Vancomycin and Cefazolin.


Eligibility criteria: Inclusion Criteria:

* Patient is scheduled to undergo an elective primary total knee arthroplasty.
* Patient is able to understand the study design and intervention and gives informed consent to participate in the study.
* Patient is 18 years or older.

Exclusion Criteria:

* Contraindication to receiving vancomycin or cefazolin.
* Body mass index (BMI) \> 40.
* Uncontrolled Diabetes (defined as A1c \> 7.5%).
* Patient received or is scheduled to receive IV vancomycin or cefazolin within 7 days prior to their planned procedure.
* Any hardware, condition, or anatomic status that prevents the tibial tubercle from being a viable intraosseous injection site.
* Refusal to participate
* Any condition, in the opinion of the primary investigator, that deems the participant unsuitable for participation in the research study.

Primary outcomes:
measure: Rate of Postoperative Infections
timeFrame: 30 days postop and 90 days postop
Secondary outcomes:
measure: Postoperative Wound Complications
timeFrame: 30 days postop and 90 days postop
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
References:
citation: Nunn MO, Corallo CE, Aubron C, Poole S, Dooley MJ, Cheng AC. Vancomycin dosing: assessment of time to therapeutic concentration and predictive accuracy of pharmacokinetic modeling software. Ann Pharmacother. 2011 Jun;45(6):757-63. doi: 10.1345/aph.1P634. Epub 2011 Jun 7.
citation: Klasan A, Patel CK, Young SW. Intraosseous Regional Administration of Vancomycin in Primary Total Knee Arthroplasty Does Not Increase the Risk of Vancomycin-Associated Complications. J Arthroplasty. 2021 May;36(5):1633-1637. doi: 10.1016/j.arth.2020.12.034. Epub 2020 Dec 26.
citation: Parkinson B, McEwen P, Wilkinson M, Hazratwala K, Hellman J, Kan H, McLean A, Panwar Y, Doma K, Grant A. Intraosseous Regional Prophylactic Antibiotics Decrease the Risk of Prosthetic Joint Infection in Primary TKA: A Multicenter Study. Clin Orthop Relat Res. 2021 Nov 1;479(11):2504-2512. doi: 10.1097/CORR.0000000000001919.
citation: Park KJ, Chapleau J, Sullivan TC, Clyburn TA, Incavo SJ. 2021 Chitranjan S. Ranawat Award: Intraosseous vancomycin reduces periprosthetic joint infection in primary total knee arthroplasty at 90-day follow-up. Bone Joint J. 2021 Jun;103-B(6 Supple A):13-17. doi: 10.1302/0301-620X.103B6.BJJ-2020-2401.R1.
citation: Chin SJ, Moore GA, Zhang M, Clarke HD, Spangehl MJ, Young SW. The AAHKS Clinical Research Award: Intraosseous Regional Prophylaxis Provides Higher Tissue Concentrations in High BMI Patients in Total Knee Arthroplasty: A Randomized Trial. J Arthroplasty. 2018 Jul;33(7S):S13-S18. doi: 10.1016/j.arth.2018.03.013. Epub 2018 Mar 15.
citation: Young SW, Zhang M, Freeman JT, Mutu-Grigg J, Pavlou P, Moore GA. The Mark Coventry Award: Higher tissue concentrations of vancomycin with low-dose intraosseous regional versus systemic prophylaxis in TKA: a randomized trial. Clin Orthop Relat Res. 2014 Jan;472(1):57-65. doi: 10.1007/s11999-013-3038-z.
citation: Harper KD, Lambert BS, O'Dowd J, Sullivan T, Incavo SJ. Clinical outcome evaluation of intraosseous vancomycin in total knee arthroplasty. Arthroplast Today. 2020 Mar 7;6(2):220-223. doi: 10.1016/j.artd.2020.02.001. eCollection 2020 Jun.
citation: Young SW, Zhang M, Freeman JT, Vince KG, Coleman B. Higher cefazolin concentrations with intraosseous regional prophylaxis in TKA. Clin Orthop Relat Res. 2013 Jan;471(1):244-9. doi: 10.1007/s11999-012-2469-2.
citation: Von Hoff DD, Kuhn JG, Burris HA 3rd, Miller LJ. Does intraosseous equal intravenous? A pharmacokinetic study. Am J Emerg Med. 2008 Jan;26(1):31-8. doi: 10.1016/j.ajem.2007.03.024.
citation: Petitpas F, Guenezan J, Vendeuvre T, Scepi M, Oriot D, Mimoz O. Use of intra-osseous access in adults: a systematic review. Crit Care. 2016 Apr 14;20:102. doi: 10.1186/s13054-016-1277-6.
citation: de Lalla F, Novelli A, Pellizzer G, Milocchi F, Viola R, Rigon A, Stecca C, Dal Pizzol V, Fallani S, Periti P. Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee replacement procedures: study of pharmacokinetics and tissue penetration. Antimicrob Agents Chemother. 1993 Dec;37(12):2693-8. doi: 10.1128/AAC.37.12.2693.
citation: Yamada K, Matsumoto K, Tokimura F, Okazaki H, Tanaka S. Are bone and serum cefazolin concentrations adequate for antimicrobial prophylaxis? Clin Orthop Relat Res. 2011 Dec;469(12):3486-94. doi: 10.1007/s11999-011-2111-8. Epub 2011 Oct 4.
citation: Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, Fish DN, Napolitano LM, Sawyer RG, Slain D, Steinberg JP, Weinstein RA; American Society of Health-System Pharmacists; Infectious Disease Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013 Feb 1;70(3):195-283. doi: 10.2146/ajhp120568. No abstract available.
citation: Sivagnanam S, Deleu D. Red man syndrome. Crit Care. 2003 Apr;7(2):119-20. doi: 10.1186/cc1871. Epub 2002 Dec 23.
citation: Feder OI, Yeroushalmi D, Lin CC, Galetta MS, Meftah M, Lajam CM, Slover JD, Schwarzkopf R, Bosco JA 3rd, Macaulay WB. Incomplete Administration of Intravenous Vancomycin Prophylaxis is Common and Associated With Increased Infectious Complications After Primary Total Hip and Knee Arthroplasty. J Arthroplasty. 2021 Aug;36(8):2951-2956. doi: 10.1016/j.arth.2021.03.035. Epub 2021 Mar 18.
citation: Classen DC, Evans RS, Pestotnik SL, Horn SD, Menlove RL, Burke JP. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med. 1992 Jan 30;326(5):281-6. doi: 10.1056/NEJM199201303260501.
citation: Peel TN, Astbury S, Cheng AC, Paterson DL, Buising KL, Spelman T, Tran-Duy A, Adie S, Boyce G, McDougall C, Molnar R, Mulford J, Rehfisch P, Solomon M, Crawford R, Harris-Brown T, Roney J, Wisniewski J, de Steiger R; ASAP Trial Group. Trial of Vancomycin and Cefazolin as Surgical Prophylaxis in Arthroplasty. N Engl J Med. 2023 Oct 19;389(16):1488-1498. doi: 10.1056/NEJMoa2301401.
citation: Liu C, Kakis A, Nichols A, Ries MD, Vail TP, Bozic KJ. Targeted use of vancomycin as perioperative prophylaxis reduces periprosthetic joint infection in revision TKA. Clin Orthop Relat Res. 2014 Jan;472(1):227-31. doi: 10.1007/s11999-013-3029-0.
citation: Burger JR, Hansen BJ, Leary EV, Aggarwal A, Keeney JA. Dual-Agent Antibiotic Prophylaxis Using a Single Preoperative Vancomycin Dose Effectively Reduces Prosthetic Joint Infection Rates With Minimal Renal Toxicity Risk. J Arthroplasty. 2018 Jul;33(7S):S213-S218. doi: 10.1016/j.arth.2018.03.009. Epub 2018 Mar 14.
citation: Siddiqi A, Forte SA, Docter S, Bryant D, Sheth NP, Chen AF. Perioperative Antibiotic Prophylaxis in Total Joint Arthroplasty: A Systematic Review and Meta-Analysis. J Bone Joint Surg Am. 2019 May 1;101(9):828-842. doi: 10.2106/JBJS.18.00990.
citation: Spangehl M. Preoperative Prophylactic Antibiotics in Total Hip and Knee Arthroplasty: What, When, and How. J Arthroplasty. 2022 Aug;37(8):1432-1434. doi: 10.1016/j.arth.2022.01.019. Epub 2022 Jan 17.
citation: Ahmed SS, Haddad FS. Prosthetic joint infection. Bone Joint Res. 2019 Dec 3;8(11):570-572. doi: 10.1302/2046-3758.812.BJR-2019-0340. eCollection 2019 Nov. No abstract available.
citation: Rodriguez-Merchan EC, Delgado-Martinez AD. Risk Factors for Periprosthetic Joint Infection after Primary Total Knee Arthroplasty. J Clin Med. 2022 Oct 18;11(20):6128. doi: 10.3390/jcm11206128.
citation: Mortazavi SM, Schwartzenberger J, Austin MS, Purtill JJ, Parvizi J. Revision total knee arthroplasty infection: incidence and predictors. Clin Orthop Relat Res. 2010 Aug;468(8):2052-9. doi: 10.1007/s11999-010-1308-6.
citation: Koh CK, Zeng I, Ravi S, Zhu M, Vince KG, Young SW. Periprosthetic Joint Infection Is the Main Cause of Failure for Modern Knee Arthroplasty: An Analysis of 11,134 Knees. Clin Orthop Relat Res. 2017 Sep;475(9):2194-2201. doi: 10.1007/s11999-017-5396-4. Epub 2017 Jun 1.