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

Hemorrhage Clinical Trial

— CONCERT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05756426
• Other study ID #: HP- 00104380
• Status: Recruiting
• Start date: April 13, 2023
• Est. completion date: January 30, 2029

Study information

• Verified date: August 2023
• Source: University of Maryland, Baltimore
• Contact: Stephen Rogers, PhD
• Phone: 410-706-7094
• Email: stephen.rogers[@]som.umaryland.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: January 30, 2029
• Est. primary completion date: January 30, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 88 Years

Eligibility

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

Related Conditions & MeSH terms

• Hemodynamic Instability
• Hemorrhage

Intervention

Other:
• Prospective
Single arm, healthy adult volunteers for blood donation.

Locations

Country	Name	City	State
United States	University of Maryland Baltimore (UMB)	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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