Clinical trial NCT05756426: Consortium for Optimized Integration of Bio-Artificial Blood Components for Adaptive Resuscitation Therapy
Official title: Consortium for Optimized Integration of Bio-Artificial Blood Components for Adaptive Resuscitation Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hemorrhage
Hemodynamic Instability
Keywords: Hemostasis
Vasoactivity
Oxygen affinity
Red Blood Cell
Whole blood analogue
Perfusion
Nitric Oxide
Methemoglobin
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2023-03-06
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

Brief 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Determine the hemoglobin based oxygen carrier (HBOC) amount in the whole blood analogue (WBA) that has the same oxygen delivery capacity as stored blood.
timeFrame: 4years
measure: Evaluate performance attributes (PA's) stored whole blood (SWB): fresh whole blood, and WBA:fresh whole blood (FWB) mixtures.
timeFrame: 4years
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Baltimore (UMB)
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Stephen Rogers, PhD
role: PRINCIPAL_INVESTIGATOR
References: