Development of Fibrin Specific Nuclear Probe to Reduce LVAD Adverse Events

Development of Fibrin Specific Nuclear Probe to Reduce LVAD Adverse Events

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R42HL139342-02
Agency Tracking Number: R42HL139342
Amount: $920,525.00
Phase: Phase I
Program: STTR
Awards Year: 2018
Solicitation Year: 2016
Solicitation Topic Code: NHLBI
Solicitation Number: PA16-303
Small Business Information
12042 GARDENGATE DR, Saint Louis, MO, 63146-4809
DUNS: 080307979
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 JAMES BLACKLEDGE
 (636) 866-8262
 james.blackledge@charter.net
Business Contact
 JUDY BALLARD
Phone: (636) 346-3140
Email: jballard@right-on-site.com
Research Institution
 WASHINGTON UNIVERSITY
 Campus Box 1054
1 Brookings Drive
SAINT LOUIS, MO, 63130-4862
 Nonprofit college or university
Abstract
Despite the myriad major advances in cardiology the prognosis for patients with severe medically refractive heart failure HF is exceedingly poor Approximately deaths occur annually in patients with HF who have endured an impaired quality of life often accompanied by significant economic and personal losses due to recurrent hospitalizations At least of these deaths were directly related to severe heart failure Because the number of available heart donors year has not increased over the last decade there is an enormous and expanding gap between medical need for transplant and the woefully low supply of hearts Todayandapos s axial and centrifugal flow left ventricular assist devices LVAD have reduced size and power requirements allowing LVADs to become a therapeutic options as a bridge to transplantation BTT and increasingly for destination therapy DT Unfortunately the life saving benefit of LVADs is offset by potential life threatening complications and costly hospital readmissions for bleeding infection and thrombosis Prophylactic anticoagulation to prevent intra pump thrombus with warfarin in addition to an anti platelet drug exacerbates inherent bleeding complications induced by the high shear high blood flow conditions of the pumps Multicenter efforts to reduce anticoagulation guidelines tripled the incidence of pump thrombotic complications LDH a nonspecific marker of RBC lysis is currently used as the best surrogate indicator for pump thrombosis But given clinical results to date LDH is only an insensitive probably late biomarker of LVAD fibrin accumulation We have innovated and demonstrated a very high avidity nuclear probe prototype mTc F A in vitro in excised LVADs operated ex vivo and in rodent models which sensitively localizes thrombus accumulation in LVADs In Phase of this Fast track proposal the effectiveness of mTc F A will be demonstrated in a large animal model calves kg using reimplanted human LVADs Kg and a clinical gamma camera In Phase the analytical chemical process and regulatory development and documentation required to transfer the product candidate FibroScint to contract research organizations for GMP toll manufacturing stability testing and GLP toxicology will be completed FibroScint is anticipated to refine and individualize LVAD clinical management to reduce bleeding events thromboembolic complications and pump exchanges !Despite the myriad major advances in cardiology the prognosis for patients with severe medically refractive HF is exceeding poor Left ventricular assist devices LVAD a mechanical circulatory support system have developed tremendously and offer considerable hope and benefit to patients with severe HF However they are associated with gastrointestinal GI bleeding driveline infections and thrombotic complications Successful LVAD outcomes require careful management of anticoagulation and the complex interplay between increased bleeding and prevention of intrapump thrombus Unfortunately multicenter efforts to lower anticoagulation goals to minimize bleeding complications resulted in a tripled incidence of pump thrombotic complications Intra pump thrombus cannot be directly diagnosed but only inferred from nonspecific evidence and these suggestive markers of pump thrombus are late findings Intrapump thrombus detected earlier may be responsive to anti thrombotic treatment or progression stabilized by improved anticoagulation Ultimately early recognition and clinical intervention could thrombotic complications and minimize surgical pump exchanges We have innovated and demonstrated a very high avidity nuclear probe prototype mTc F A in vitro in excised LVADs operated ex vivo and in rodent models which sensitively localizes thrombus accumulation in LVADs In Phase of this Fast track proposal the effectiveness of mTc F A will be demonstrated in a large animal model calves kg using re implanted human LVADs Kg and a clinical gamma camera In Phase the analytical chemical process and regulatory development and documentation required to transfer the product candidate FibroScint to contract research organizations for GMP toll manufacturing stability testing and GLP toxicology will be completed FibroScint is anticipated to refine and individualize LVAD clinical management to reduce bleeding events thromboembolic complications and pump exchanges

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

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