Antibiotic Concentrations After MassivE Transfusion Study (ACME)

February 7, 2025 updated by: Steven Schauer, Brooke Army Medical Center

Antibiotic Concentrations After MassivE Transfusion (ACME) Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

417

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital
        • Contact:
        • Principal Investigator:
          • Adit A Ginde, M.D., M.P.H
    • Texas
      • Fort Sam Houston, Texas, United States, 78234

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Trauma patients brought to study sites who receive an antibiotic during their index hospitalization.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control Group
Patients who ideally receive no blood but may be included if they receive up to 2 units of transfused blood.
Other: Control Group
This group consists of trauma patients who receive minimal or no blood transfusions (up to 2 units of blood). Blood samples are also collected at six designated timepoints after antibiotic administration to measure plasma antibiotic concentrations. As with the massive transfusion group, clinical draws will be coordinated whenever possible to obtain research samples, with a maximum of two dedicated research-only draws if needed. Data analysis will compare antibiotic concentration trends in this group with those in the massive transfusion group to understand the effects of blood transfusion volume on antibiotic pharmacokinetics.
Massive Transfusion Group
Patients who receive at least 3 units of blood.
Other: Massive Transfusion Group
This group includes trauma patients who receive a massive transfusion, defined as the transfusion of at least 3 units of blood. Blood samples are collected at six specific timepoints following the administration of antibiotics to analyze plasma antibiotic concentrations. Existing clinical draws will be used whenever possible to minimize additional venipunctures, with a maximum of two dedicated research-only draws allowed if necessary. Data analysis will assess the impact of large blood transfusions on antibiotic pharmacokinetics over time, adjusting for factors such as kidney function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Amount of drug concentrations within first 18 hours.
Time Frame: From initial enrollment until 30 days after.
Obtain drug concentrations at regular intervals during the first 18 hours after antibiotic administration.
From initial enrollment until 30 days after.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total volume of blood products within 24 hours.
Time Frame: 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.
From initial enrollment until 30 days after.
Correlation Between Blood Transfusion Volume and Drug Concentration Levels
Time Frame: 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).
Through study completion, an average of 3 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brooke Army Medical Center

Collaborators

Congressionally Directed Medical Research Programs
The Metis Foundation
University of Colorado Health

Investigators

  • Principal Investigator: Julie A Rizzo, MD, Brooke Army Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 30, 2024

Primary Completion (Estimated)

July 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

October 31, 2024

First Submitted That Met QC Criteria

November 18, 2024

First Posted (Actual)

November 21, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 7, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Other Study ID Numbers

  • 23-2559
  • HT9425-23-1-1074 (Other Grant/Funding Number: CDMRP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

IPD sharing is not authorized without a written agreement with the Defense Health Agency.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe