Antibiotic Concentrations After MassivE Transfusion Study

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorBrooke Army Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Receives ampicillin/sulbactam, cefazolin, cefepime, ceftriaxone, clindamycin, ertapenem, levofloxacin, metronidazole or pipercillin/tazobactam at any dose

Hospitalized or anticipated hospital admission

Disqualifiers

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

Trial population

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

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

  • Massive Transfusion Group

    Other intervention

    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.

  • Control Group

    Other intervention

    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.

Treatment groups

417 Participants
are divided into 2 treatment groups
Group A: Control Group1 intervention
Group B: Massive Transfusion Group1 intervention

Trial outcomes

Primary outcomes

1

Amount of drug concentrations within first 18 hours.

Obtain drug concentrations at regular intervals during the first 18 hours after antibiotic administration.

Time frame
From initial enrollment until 30 days after.

Secondary outcomes

1

Total volume of blood products within 24 hours.

Determine the total volume of blood products and fluids transfused during the first 24 hours after antibiotic administration.

Time frame
From initial enrollment until 30 days after.
2

Correlation Between Blood Transfusion Volume and Drug Concentration Levels

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).

Time frame
Through study completion, an average of 3 years.

Other outcomes

Sponsors and contacts

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Brooke Army Medical Center

Lead sponsor

Congressionally Directed Medical Research Programs

Collaborator

The Metis Foundation

Collaborator

University of Colorado Health

Collaborator