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Rapid Test to Assist Therapy in Neonatal Sepsis and Necrotizing Enterocolitis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R44AI141283-02
Agency Tracking Number: R44AI141283
Amount: $1,862,493.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: R
Solicitation Number: PA17-302
Solicitation Year: 2017
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-05-03
Award End Date (Contract End Date): 2021-04-30
Small Business Information
Providence, RI 02903-4204
United States
DUNS: 140315248
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (401) 301-2046
Business Contact
Phone: (401) 301-2046
Research Institution

The primary goal of this proposed research is to develop a rapid point-of-care test that assesses the
risk of neonatal sepsis (NS) and/or necrotizing enterocolitis (NEC) in infants based on Inter-alpha inhibitor
proteins (IAIP) levels in blood. The test is expected to be simple, user-friendly, portable and suitable for use in
the NICU. NS and NEC are associated with high mortality and morbidity, including adverse neuro-
developmental outcomes. Furthermore, both conditions are associated with systemic inflammatory responses
and their initial clinical presentations are similar, non-specific and subtle leading to a greater likelihood for
misdiagnosis. It is important for clinicians to discern which patients are at risk for progressing to NEC or NS as
clinical deterioration in both diseases can progress in a fulminant manner resulting in shock and death within
hours of clinical presentation. There is currently no sensitive and specific test for early detection of NS and
NEC. IAIP are found in plasma at a relatively high concentration and play an important role as innate immunity
proteins to modulate host inflammatory response to pathological insults. During acute systemic inflammation
following severe infection, trauma and injury, these proteins are rapidly depleted leading to a rapid decrease in
plasma levels. We previously reported that IAIP levels are significantly decreased in adult sepsis and in infants
with NS and NEC. In our recently completed studies, we confirmed that IAIP level is a sensitive and specific
predictive marker for NS and NEC and more remarkably, the IAIP test has excellent high negative predictive
value in both NS (98%) and NEC (100%) indicating that this test is potentially useful to influence the judgment
on whether or not to discontinue antimicrobial treatment when the conventional tests are uninformative.
Furthermore, our results demonstrated that it is feasible to develop a quantitative lateral flow-based test that is
capable of measuring IAIP within 15 min. which is comparable to the results obtained by our 6 hr. laboratory
based competitive ELISA (R2andgt;0.8). In this proposal, we will extend these studies to improve the rapid assay
design and further optimize the prototype test toward a fully developed product through design verification and
design validation using clinical samples collected from infants suspected with NS and NEC at multiple clinical
sites. The specific aims of the Fast track SBIR project are: 1) Feasibility study to convert the competitive rapid
lateral flow assay to a more robust and improved “sandwich” rapid IAIP assay format; 2) Design verification
study of the lateral flow IAIP rapid test; 2) Integration of the IAIP rapid test strip with the reader system and 4)
Cross verification studies of the IAIP rapid test performance and confirmation studies of its predictive value
using collected clinical samples. These studies are designed to obtain a robust and fully developed prototype
test that is ready to enable future studies required for regulatory approval by the FDA. The impact of this
project is immense as the rapid test will help reduce the high morbidity and mortality associated with the
devastating diseases of NS and NEC as well as support antibiotic stewardship in infants.The goal of this proposed research is to develop a rapid test based on Inter-alpha inhibitor proteins that
can be useful to detect infants with life-threatening conditions such as whole body infection (sepsis) and
necrotizing enterocolitis using a simple, portable device suitable for a bedside testing. The potential
impact of the proposed research is immense as it will reduce the devastating effects of these diseases.

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

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