Antibiotic Concentrations After MassivE Transfusion Study

NCT ID: NCT06699901

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 417 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2027-09-30

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.

Conditions

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Control Group

Patients who ideally receive no blood but may be included if they receive up to 2 units of transfused blood.

Control Group

Intervention Type: OTHER

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.

Massive Transfusion Group

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

The Metis Foundation

OTHER

Sponsor Role: collaborator

University of Colorado Health

OTHER

Sponsor Role: collaborator

Brooke Army Medical Center

FED

Sponsor Role: lead

Responsible Party

Steven Schauer

PRINCIPAL INVESTIGATOR

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julie A Rizzo, MD

Role: PRINCIPAL_INVESTIGATOR

Brooke Army Medical Center

Locations

University of Colorado Hospital

Aurora, Colorado, United States

Site Status: RECRUITING

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Steven G Schauer, DO

Role: CONTACT

steven.g.schauer.mil@army.mil

2109160808

Jessica Mendez, MS

Role: CONTACT

jessica.mendez32.ctr@health.mil

Facility Contacts

Erin Anderson L Research Services Program Manager, RN

Role: primary

erin.l.anderson@cuanschutz.edu

720-999-8760

Jessica Mendez, M.S.

Role: primary

jessica.mendez32.ctr@health.mil

210-916-0808

Steven G Schauer, DO,MS,RDMS

Role: backup

steven.g.schauer.mil@army.mil

2109160808

References

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.

Reference Type: BACKGROUND

PMID: 33937714 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32969008 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21795876 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33760684 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34741519 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29067429 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23192066 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HT9425-23-1-1074

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

23-2559

Identifier Type: -

Identifier Source: org_study_id