Consortium for Optimized Integration of Bio-Artificial Blood Components for Adaptive Resuscitation Therapy (CONCERT)

There is need for a whole blood analog for use when banked blood is unavailable or undesirable.

In civilian trauma, hemorrhage accounts for ~ 35% of pre-hospital deaths; moreover, ~ 20% of military casualties are in hemorrhagic shock on arrival to field hospitals and an additional 5% require urgent transfusion. A recent review concluded that hemorrhage accounted for ~ 90% of potentially survivable battlefield deaths - lives that could be saved with better hemorrhage control capabilities and improved, field-ready blood, blood components, or blood substitutes. While study of ideal composition for resuscitative fluids is ongoing, it is evident that for those in hemorrhagic shock, volume replenishment alone (without O2 carrying capacity) is insufficient. Alternatively, with massive blood loss or with ongoing bleeding from non-compressible injuries, resuscitation with an O2 carrier alone may be complicated by acquired coagulopathy (either dilutional or trauma-induced).

Development of a balanced resuscitation fluid that treats both shock and coagulopathy (comprising a field-deployable O2 carrier with lyophilized humoral hemostatic components and platelets) is essential to allow on-scene treatment during the critical 'golden-hours' after injury. As such, the whole blood analog described herein could be this product, thus transforming care in both civilian and military settings.The scientific purpose of this study is to develop a combined whole blood substitute from individual artificial prototypes that have been separately developed for each blood component (i.e., combining an artificial oxygen carrier, with an artificial plasma analogue and an artificial platelet analogue). Together, these combined components will recapitulate the composition and performance of natural whole blood.

Blending and combination experiments of the individual artificial prototypes will be performed to test compatibility and optimize efficacy. State of the art in vitro (bench top) assays will be performed to assess physicochemical and functional performance (hemodynamics, oxygen delivery, hemostasis), with data being compared to experiments performed on fresh and stored whole blood.

Study Overview

• Status: Recruiting
• Conditions: Hemorrhage; Hemodynamic Instability
• Intervention / Treatment: Other: Prospective

Detailed Description

Previous blood substitutes have failed for 3 main reasons. (1) dysfunctional oxygen interactions resulting from fixed oxygen affinity, allowing adequate oxygen capture in the lungs, but poor oxygen release to tissue (i.e., oxygen affinity is not context responsive to physiologic cues of perfusion sufficiency such as pH, etc.), (2) interference with normal regulation of blood vessel caliber, with inappropriate trapping of the endogenous vasodilator nitric oxide resulting in intense vasoconstriction and tissue ischemia, and (3) inability to maintain hemoglobin functionality during circulation, with hemoglobin auto-oxidizing to methemoglobin which cannot carry and deliver oxygen, thus resulting in a drastically limited effective circulation time.

The individual artificial blood components, which will form the whole blood analog in this proposal, have been designed to overcome these previous design flaws. In addition, all components are amenable to facile reconstitution after extended, ambient dry storage, allowing sustained shelf stability.

In short, these components are ripe for integration to form a product recapitulating natural blood performance.

This study will use data and specimens collected under this protocol and will prospectively enroll new subjects at UMB for observational study. There will not be issues related to the probability of group assignment, the potential for subject to be randomized to a placebo group or the use of controlled substances.

There is only one cohort involved in this study

1. Prospective healthy adults (UMB only)

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Stephen Rogers, PhD; Phone Number: 410-706-7094; Email: stephen.rogers@som.umaryland.edu
• Study Contact Backup: Name: Tobi Rowden, RN; Phone Number: 410-706-7094; Email: trowden@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland Baltimore (UMB)
      • Contact: Stephen Rogers, PhD; Email: stephen.rogers@umaryland.som.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This research study intends to enroll 50healthy volunteer subjects/year over the next 5 years (total of 250 subjects).

Description

Inclusion Criteria:

• Subject >/= 18 years of age
• Subject weighs >40kg (88lbs)
• Subject must be generally healthy

Exclusion Criteria:

• Suspected or diagnosed with ongoing (chronic) or acute infection
• Subject is pregnant
• Subject is non-english speaking

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers; Healthy Volunteers >/= 18yrs of age without acute or chronic illness.	Other: Prospective; Single arm, healthy adult volunteers for blood donation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the hemoglobin based oxygen carrier (HBOC) amount in the whole blood analogue (WBA) that has the same oxygen delivery capacity as stored blood.	Oxygen delivery capacity will be analyzed by measuring the oxygen disassociation curve and determining and arterial-venous (A-V) delta hemoglobin oxygen saturation. From this an A-V oxygen flux capacity can be determine and matched between stored blood and HBOC.	4years
Evaluate performance attributes (PA's) stored whole blood (SWB): fresh whole blood, and WBA:fresh whole blood (FWB) mixtures.	Compose mixtures of SWB:FWB or WBA:FWB, in ratios consistent of massive transfusions. Quantify (1) oxygen disassociation curve of mixtures across pH ranges of stressed physiology (pH 7.2-7.6). Determine the A-V delta hemoglobin saturation to calculate oxygen flux capacity. (2) viscosity shear relationships and visco elastic behavior will be characterized by rheometry, (3) Nitric oxide (NO) trapping and vasoactivity utilizing a biochemical NO trapping assay and a aortic rings (vascular ring bioassay), (4) hemostasis measuring thromboelastography (TEG).	4years

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Stephen Rogers, PhD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2029

Study Registration Dates

• First Submitted: February 2, 2023
• First Submitted That Met QC Criteria: February 23, 2023
• First Posted (Actual): March 6, 2023

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Hemostasis; Red Blood Cell; Nitric Oxide; Perfusion; Methemoglobin; Vasoactivity; Oxygen affinity; Whole blood analogue
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hemorrhage; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Epidemiologic Studies; Epidemiologic Study Characteristics; Cohort Studies; Longitudinal Studies
• Other Study ID Numbers: HP- 00104380

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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