Acute kidney injury (AKI) and septic shock associated AKI (SSAKI) requiring renal replacement therapy (RRT) are significant complications in intensive care unit (ICU) patients with an associated mortality rate exceeding 50%. The need for novel therapeutics that are specifically approved for pediatric AKI/RRT use is driven by the nearly 50% mortality rates of pediatric patients with this disorder. The SCD is a novel device containing bundled biomimetic polysulfone fibers which selectively bind/sequester and deactivate leukocytes (LE) in a dialysis extracorporeal blood circuit, resulting in an immunomodulatory effect in the systemic inflammatory response associated with AKI and SSAKI. The SCD, combined with regional citrate anticoagulation, is a novel therapeutic application utilizing biocompatible membranes that allow LE attachment in a calcium low environment during regional citrate anticoagulation resulting in a diminution in the LE activated state. The SCD has been studied in prior clinical trials of AKI. This proposal will study the safety and efficacy of SCD therapy in pediatric patients with AKI requiring CRRT therapy.
Specific Aim 1 will evaluate this innovative approach in pediatric ICU patients of greater than 20 kilograms (kg) in body weight.
Specific Aim 2 will assess this approach in pediatric patients with body weights between 8 and 20 kg utilizing a SCD one-fifth the size of the current SCD.

Public Health Relevance

INTRODUCTION AND PROJECT NARRATIVE. The goal of this proposal is to provide safety and early efficacy data on therapy using a selective cytopheretic device (SCD), an extracorporeal membrane device that can sequester activated leukocytes and inhibit their inflammatory activity in order to reduce tissue accumulation and resulting tissue damage in patients. The SCD will be evaluated use in pediatric ICU patients that have acute kidney injury or septic shock associated acute kidney injury requiring renal replacement therapy. There is nearly a 50% mortality rate of pediatric patients with this disorder. The lack of medical devices specifically designed for pediatric applications has been recognized by directives in the Pediatric Medical Device Safety and Improvement Act of 2007, included in Public Law 110-85, and the Institutes of Medicine, which has recommended pediatric studies to begin at the end of Phase II clinical trials involving adults Inflammatory. The relevance of this proposal to public health is that the SCD would greatly reduce the multiorgan effects in pediatric patients suffering from acute kidney injury or septic shock associated acute kidney injury, thus improving the clinical outcome of these pediatric patients affected by these disease processes.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
5R01FD005092-02
Application #
9139398
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1)1)
Project Start
2015-09-10
Project End
2020-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
2
Fiscal Year
2017
Total Cost
$399,483
Indirect Cost
Name
Innovative Biotherapies, Inc.
Department
Type
Domestic for-Profits
DUNS #
143681240
City
Ann Arbor
State
MI
Country
United States
Zip Code
48108
Selewski, David T; Goldstein, Stuart L; Fraser, Erin et al. (2017) Immunomodulatory Device Therapy in a Pediatric Patient With Acute Kidney Injury and Multiorgan Dysfunction. Kidney Int Rep 2:1259-1264