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Novel Extracorporeal Therapy for the Reversal of Septic Shock and Restoring Hemodynamic Stability

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43GM144973-01
Agency Tracking Number: R43GM144973
Amount: $281,835.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 300
Solicitation Number: PA20-260
Solicitation Year: 2020
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-09-01
Award End Date (Contract End Date): 2023-04-30
Small Business Information
Monmouth Junction, NJ 08852-1977
United States
DUNS: 830014077
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (732) 329-8885
Business Contact
Phone: (813) 766-8091
Research Institution

Rationale: Sepsis has been classified by the World Health Organization as a “global health priority.” It has been
estimated that ~50% of patients with sepsis due to Gram-negative bacteria will develop septic shock and of these, half
may die. There are currently no treatment options for attenuating the elevated inflammatory response and hemodynamic
instability that is present in these patients. Therapy is mainly supportive and limited to a combination of vasopressors,
intravenous fluid, and antibiotics. The role of bacterial endotoxin in modulating the level of host-derived inflammatory
mediators, including cytokines, chemokines, and complement factors, and their contribution to septic shock is widely
reported in literature. When in excess, these mediators can induce organ dysfunction, multiorgan failure, and even death.
Innovation: Use CytoSorb, a CE Mark approved extracorporeal cytokine filter, together with a novel endotoxin adsorber,
LPSorb, to reduce both the trigger and causative agents of cytokine storm and hemodynamic instability in septic shock.
Hypothesis: CytoSorb combined with LPSorb attenuates excessive levels of inflammatory mediators and reduces levels
of endotoxin in septic plasma.
Specific Aims: 1) Characterize the endotoxin and inflammatory cytokine expression profile in plasma from septic pigs
during the development of septic shock and acute respiratory distress. 2a-c) Evaluate cytokine and endotoxin removal
ability and the impact on plasma pH, electrolytes, intrinsic and extrinsic coagulation pathways and albumin levels of
CytoSorb therapy, LPSorb therapy, and CytoSorb+LPSorb in plasma from septic pigs in a benchtop recirculation system.
Study Design: The focus of Aim 1 is to characterize changes in levels of key sepsis-associated inflammatory cytokines
and bacterial endotoxin in circulation during the onset of septic shock in this highly clinically relevant swine sepsis model
in order to draw correlations between the inflammatory status and loss of hemodynamic stability leading up to multiple
organ failure and death. Pigs (35kg) will be subjected to a ‘2-hit’ surgical procedure involving fecal clot implantation in
the peritoneal cavity, followed by transient clamping of the superior mesenteric artery to induce septic shock and acute
respiratory distress syndrome (ARDS). Blood samples will be taken before the procedure and every 6 hours after until the
terminal bleed at 36 hours. Metrics will include vitals (BT, BP, HR, RR), complete blood counts, blood chemistries, and
cytokine and endotoxin concentrations. In Aim 2a-c, CytoSorb, LPSorb, and CytoSorb+LPSorb devices will be evaluated
in a scaled-down benchtop recirculation system for cytokine and endotoxin removal capacity and any potential impact the
therapy may have on plasma coagulation and albumin content in septic pig plasma taken 36 hours after the ‘2-hit’
procedure. Metrics will include cytokine and endotoxin concentrations, PT, aPTT, uPTT, and albumin level.
Impact and Translation: If successful, this study will confirm the feasibility of implementing CytoSorb + LPSorb as a
definitive treatment for septic shock and hemodynamic instability. Pending positive outcomes in future preclinical and
clinical studies, this innovative sepsis treatment will provide a highly effective means of controlling life-threatening
hyperinflammation during the early stages of septic shock, with the potential to dramatically improve survival.

* Information listed above is at the time of submission. *

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