Clinical trial NCT06699901: Antibiotic Concentrations After MassivE Transfusion Study
Official title: Antibiotic Concentrations After MassivE Transfusion (ACME) Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood Constituents
Lead sponsor: Brooke Army Medical Center
Sponsor class: FED
Collaborators: name: Congressionally Directed Medical Research Programs
name: The Metis Foundation
name: University of Colorado Health
First posted: 2024-11-21
Enrollment: 417
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Trauma patients brought to study sites who receive an antibiotic during their index hospitalization.

Brief summary: Combat and civilian trauma frequently result in open wounds that are at risk for infection. Data from the Department of Defense Trauma Registry demonstrate that 74% of combat trauma casualties have an open wound. The Committee on Tactical Combat Casualty Care, the Prolonged Field Care Working Group, and the Joint Trauma System clinical practice guidelines recommend antibiotic prophylaxis for open wounds after trauma. The civilian setting has similar risks of open wound infection after trauma. In parallel, current practice guidelines recommend the aggressive use of balanced blood products during resuscitation. It remains unclear how the replacement of blood after hemorrhage through transfusion may affect antibiotic concentrations. Data is necessary to better understand this relationship to enhance wound prophylaxis antibiotic dosing, particularly in severely wounded casualties who receive blood products during massive transfusions. It remains unclear how these resuscitation methods may alter pharmacokinetics. The investigators hypothesize that drug concentrations decrease in direct relation to the amount of blood transfused during low-volume, massive, and supermassive transfusion after trauma compared to patients who receive no blood products. The investigators seek to understand the relationship between drug concentrations and blood product administration using a non-compartmentalized model in the setting of hemorrhage. Specifically, they will (1) obtain drug concentrations at regular intervals during the first 12-18 hours after administration of antibiotics, (2) determine how much blood products and fluids are transfused during the 12 hours prior to antibiotic and 24 hours post-administration, and (3) perform data modeling to understand the relationship between blood transfusions and drug concentrations to inform data-driven dosing models. Liquid chromatography methods will be developed to measure drug concentrations. The investigators will conduct a prospective, multicenter study at two large trauma centers - Brooke Army Medical Center and the University of Colorado Hospital. They will seek to enroll any participant who is hospitalized or anticipated hospital admission for acute trauma and receives an antibiotic on the study list during their index hospitalization. They will then model the drug levels against the amount of blood and fluid infused to create an understanding of the pharmacokinetics of antibiotic wound prophylaxis.

Detailed description: This observational study evaluates the impact of blood transfusion volume on antibiotic plasma concentration in trauma patients. Participants who meet trauma criteria in the ED and receive specified antibiotics during their hospitalization are identified through trauma alerts, clinical engagement, and pharmacist involvement. A convenience sample will be enrolled, aiming for a 1:2 ratio of transfused patients to controls. Blood samples (1mL per timepoint) will be taken at six intervals post-antibiotic infusion, often aligning with clinical draws to minimize additional venipunctures. Samples will be processed, stored, and shipped to the USAISR lab for analysis, with data entered into REDCap for de-identified storage and future analysis. Statistical methods include descriptive and inferential statistics, regression modeling, ANOVA, and regression analysis to assess concentration differences by transfusion status and volume. Data is secured under HIPAA regulations, and minimal additional risk qualifies the study for a waiver of informed consent.

Eligibility criteria: Inclusion Criteria:

* Receives ampicillin/sulbactam, cefazolin, cefepime, ceftriaxone, clindamycin, ertapenem, levofloxacin, metronidazole or pipercillin/tazobactam at any dose
* Hospitalized or anticipated hospital admission

Exclusion Criteria:

* Received the same antibiotic within the past 5 half-lives of the drug (e.g. received the same antibiotic during a recent interval)
* \<18 years of age
* Known pregnancy
* Known Prisoner

Primary outcomes:
measure: Amount of drug concentrations within first 18 hours.
timeFrame: From initial enrollment until 30 days after.
Secondary outcomes:
measure: Total volume of blood products within 24 hours.
timeFrame: From initial enrollment until 30 days after.
measure: Correlation Between Blood Transfusion Volume and Drug Concentration Levels
timeFrame: Through study completion, an average of 3 years.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
Study officials:
affiliation: Brooke Army Medical Center
name: Julie A Rizzo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burbank KM, Schauer SG, De Lorenzo RA, Wenke JC. Early application of topical antibiotic powder in open-fracture wounds: A strategy to prevent biofilm formation and infections. OTA Int. 2020 Oct 12;3(4):e091. doi: 10.1097/OI9.0000000000000091. eCollection 2020 Dec.
citation: Schauer SG, Naylor JF, Ahmed YM, Maddry JK, April MD. Prehospital Combat Wound Medication Pack Administration in Iraq and Afghanistan: A Department of Defense Trauma Registry Analysis. J Spec Oper Med. 2020 Fall;20(3):76-80. doi: 10.55460/X4E8-NNXE.
citation: Eastridge BJ, Hardin M, Cantrell J, Oetjen-Gerdes L, Zubko T, Mallak C, Wade CE, Simmons J, Mace J, Mabry R, Bolenbaucher R, Blackbourne LH. Died of wounds on the battlefield: causation and implications for improving combat casualty care. J Trauma. 2011 Jul;71(1 Suppl):S4-8. doi: 10.1097/TA.0b013e318221147b.
citation: Schauer SG, Naylor JF, Fisher AD, April MD, Hill R, Mdaki K, Becker TE, Bebarta VS, Bynum J. An Analysis of 13 Years of Prehospital Combat Casualty Care: Implications for Maintaining a Ready Medical Force. Prehosp Emerg Care. 2022 May-Jun;26(3):370-379. doi: 10.1080/10903127.2021.1907491. Epub 2021 Apr 16.
citation: Fisher AD, Lavender JS, April MD, Hill R, Bynum J, Schauer SG. A Descriptive Analysis of Supermassive Transfusion Recipients Among US and Coalition Forces During Combat Operations in Afghanistan and Iraq. Mil Med. 2023 May 16;188(5-6):e1022-e1027. doi: 10.1093/milmed/usab455.
citation: Shackelford SA, Del Junco DJ, Powell-Dunford N, Mazuchowski EL, Howard JT, Kotwal RS, Gurney J, Butler FK Jr, Gross K, Stockinger ZT. Association of Prehospital Blood Product Transfusion During Medical Evacuation of Combat Casualties in Afghanistan With Acute and 30-Day Survival. JAMA. 2017 Oct 24;318(16):1581-1591. doi: 10.1001/jama.2017.15097.
citation: Eastridge BJ, Mabry RL, Seguin P, Cantrell J, Tops T, Uribe P, Mallett O, Zubko T, Oetjen-Gerdes L, Rasmussen TE, Butler FK, Kotwal RS, Holcomb JB, Wade C, Champion H, Lawnick M, Moores L, Blackbourne LH. Death on the battlefield (2001-2011): implications for the future of combat casualty care. J Trauma Acute Care Surg. 2012 Dec;73(6 Suppl 5):S431-7. doi: 10.1097/TA.0b013e3182755dcc.