Antibiotic Concentrations After MassivE Transfusion Study

Recruiting

• Conditions: Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood Constituents

• Registration Number: NCT06699901
• Lead Sponsor: Brooke Army Medical Center

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.

Study Timeline

• Study Start: 2024-09-30
• Study First Submitted: 2024-10-31
• Study First Submitted QC: 2024-11-18
• Study First Posted: 2024-11-21
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-07
• Last Update Posted: 2025-02-11
• Primary Completion: 2027-07-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 417

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Amount of drug concentrations within first 18 hours.	From initial enrollment until 30 days after.	Obtain drug concentrations at regular intervals during the first 18 hours after antibiotic administration.

Secondary Outcome Measures

Name	Time	Method
Total volume of blood products within 24 hours.	From initial enrollment until 30 days after.	Determine the total volume of blood products and fluids transfused during the first 24 hours after antibiotic administration.
Correlation Between Blood Transfusion Volume and Drug Concentration Levels	Through study completion, an average of 3 years.	Assess the correlation between the volume of blood transfusions administered and resulting drug concentration levels. Blood transfusion volume will be recorded in milliliters (mL), and drug concentration levels will be measured in nanograms per milliliter (ng/mL) using Liquid Chromatography/Tandem Mass Spectrometry Methods (LC-MS/MS).

Trial Locations

Locations (2)

Brooke Army Medical Center; 🇺🇸 Fort Sam Houston, Texas, United States

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States