This Clinical Center (Prairieland Consortium) is a collaborative effort among the Pediatric Cardiovascular Programs at Cincinnati Children's Hospital Medical Center, Cincinnati, OH and Riley Hospital for Children, Indianapolis, IN. Previous experience in the Pediatric Heart Network (PHN), an outstanding research team and the Consortium's combined patient population, characterized by >500 open heart surgeries and >20,000 echocardiograms annually, support an ability to contribute significantly to patient recruitment for PHN trials. The Clinical Trial we propose addresses an important gap in clinical medicine by translating bench discovery of biomarker technology into a pediatric multicenter clinical trial. Acute kidney injury (AKI) is a common complication of cardiopulmonary bypass (CPB), affecting adult and pediatric patients and significantly increasing the risk of mortality and medical services utilization. AKI treatment has traditionally been limited to supportive care or renal replacement therapy for severe cases. A major reason for treatment failure has been the unavoidable delay in initiating treatment secondary to lack of early biomarkers for AKI, akin to troponins in acute myocardial injury. Our research team identified neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic biomarker and showed that plasma and urine NGAL levels 2 hours after initiation of CPB reliably predict AKI development. Availability of a point-of-care (POC) NGAL test provides a means to diagnose AKI risk within an appropriate therapeutic """"""""window of opportunity"""""""". Our central hypothesis is that early treatment of pediatric patients at risk for AKI based upon NGAL POC testing will reduce the incidence or mitigate the severity of AKI following CPB. We propose a randomized, double-blind trial comparing sodium bicarbonate (NaHCO3), the anti-oxidant N-acetylcysteine (NAC) or combination therapy to placebo in post-CPB pediatric patients, ages 1 month to 18 years, at risk for AKI based on early elevation of plasma NGAL. Assuming the participation of all 8 core PHN Centers with a conservative estimated minimum yearly volume of 200-250 eligible patients and a consent rate of 50%, study enrollment would be completed in 18- 23 months, allowing for analysis and dissemination of results within a 3 year time period.
AKI is relevant to public health as it is a common, clinically significant problem following CPB in patients of all ages. Use of a biomarker for assessment of AKI risk provides for the first time an opportunity for early intervention to reduce the incidence or mitigate the severity of AKI following CPB and thereby prevent associated morbidity and mortality. Thus, the proposed research is relevant to NIH's mission because it will provide fundamental knowledge necessary to reduce illness burden from AKI.
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