Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood ConstituentsACMENCT06699901
Antibiotic Concentrations After MassivE Transfusion Study
An observational study of Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood Constituents, run by Brooke Army Medical Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood Constituents
- What is being tested?
- Massive Transfusion Group
- How many people
- 417 participants
- Where
- 2 sitesUnited States
- Study dates
- 30 Sep 2024to 30 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Trauma patients brought to study sites who receive an antibiotic during their index hospitalization.
Who may be able to join
- Receives ampicillin/sulbactam, cefazolin, cefepime, ceftriaxone, clindamycin, ertapenem, levofloxacin, metronidazole or pipercillin/tazobactam at any dose
- Hospitalized or anticipated hospital admission
Who cannot join
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Jessica Mendez, MS contact
United States2 sites, 2 recruiting
- Recruiting
University of Colorado Hospital
Aurora, Colorado, 80045
Erin Anderson L Research Services Program Manager, RN, 720-999-8760, erin.l.anderson@cuanschutz.edu
Adit A Ginde, M.D., M.P.H
- Not yet recruiting
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
Jessica Mendez, M.S., 210-916-0808, jessica.mendez32.ctr@health.mil
Steven G Schauer, DO,MS,RDMS, 2109160808, steven.g.schauer.mil@army.mil
About this study
Official title: 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.
Read the 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
- Being tested
- Massive Transfusion Group, Control Group
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Massive Transfusion GroupOther
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 GroupOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Control Group | Patients who ideally receive no blood but may be included if they receive up to 2 units of transfused blood. Receives: Other: Control Group | |
| Massive Transfusion Group | Patients who receive at least 3 units of blood. Receives: Other: Massive Transfusion Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amount of drug concentrations within first 18 hours.
Obtain drug concentrations at regular intervals during the first 18 hours after antibiotic administration.
Measured: From initial enrollment until 30 days after.
Secondary outcomes (2)
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.
Measured: From initial enrollment until 30 days after.
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).
Measured: Through study completion, an average of 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2024
- Study start30 Sep 2024
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood ConstituentsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 417 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brooke Army Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Congressionally Directed Medical Research Programs, The Metis Foundation, University of Colorado Health
- Responsible party
- Principal investigator, Steven Schauer, Brooke Army Medical Center
- Investigators
- Julie A Rizzo, MD, Principal investigator, Brooke Army Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06699901
- Sponsor's protocol ID
- 23-2559
- Other IDs
- HT9425-23-1-1074
- Acronym
- ACME
- Status last verified
- Feb 2025
- First submitted
- 31 Oct 2024
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD sharing is not authorized without a written agreement with the Defense Health Agency.
Publications
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.
PubMed 33937714Schauer 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.
PubMed 32969008Eastridge 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.
PubMed 21795876Schauer 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.
PubMed 33760684Fisher 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.
PubMed 34741519Shackelford 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.
PubMed 29067429Eastridge 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.
PubMed 23192066
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antibiotic Concentrations After MassivE Transfusion (ACME) Study
- ClinicalTrials.gov ID
- NCT06699901
- Acronym / sponsor ID
- ACME / 23-2559
- Conditions
- Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood Constituents
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 417 participants (estimated)
- Lead sponsor
- Brooke Army Medical CenterUS federal agency
- Collaborators
- Congressionally Directed Medical Research Programs, The Metis Foundation, University of Colorado Health
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 21 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | – | Other: Control GroupPatients who ideally receive no blood but may be included if they receive up to 2 units of transfused blood. |
| Massive Transfusion Group | – | Other: Massive Transfusion GroupPatients who receive at least 3 units of blood. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Trauma patients brought to study sites who receive an antibiotic during their index hospitalization.
Key inclusion criteria (2 listed)
- Receives ampicillin/sulbactam, cefazolin, cefepime, ceftriaxone, clindamycin, ertapenem, levofloxacin, metronidazole or pipercillin/tazobactam at any dose
- Hospitalized or anticipated hospital admission
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Massive Transfusion GroupThis 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. | Other | Massive Transfusion Group |
| Control GroupThis 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. | Other | Control Group |
Primary outcome
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.
2 secondary outcomes
Total volume of blood products within 24 hours.
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Background: PubMed 33937714Burbank 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.
- Background: PubMed 32969008Schauer 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.
- Background: PubMed 21795876Eastridge 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.
- Background: PubMed 33760684Schauer 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.
- Background: PubMed 34741519Fisher 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.
- Background: PubMed 29067429Shackelford 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.
- Background: PubMed 23192066Eastridge 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.
- Individual participant dataSharing planned: No. IPD sharing is not authorized without a written agreement with the Defense Health Agency.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jessica Mendez, MS contact
Julie A Rizzo, MD principal investigator
Brooke Army Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adverse Effects in the Therapeutic Use of Other and Unspecified Agents Affecting Blood Constituents, run by Brooke Army Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Steven G Schauer, DO (2109160808, steven.g.schauer.mil@army.mil), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amount of drug concentrations within first 18 hours. (time frame: From initial enrollment until 30 days after.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06699901, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2025.