The TARGET Trial:
A POC-AKI Multicenter Nexus Collaborative

The TARGET Trial is a Point-of-Care Acute Kidney Injury (POC-AKI) multicenter collaboration of pediatric Acute Kidney Injury (AKI) clinical research hospitals whose intent is to demonstrate similar survival and ICU length of stay improvements across a multicenter endeavor, while building a persistent real-time collaborative data continuum to further clinical research in the area of pediatric critical care.

Epidemiology & Motivation

Acute kidney injury (AKI) is a common clinical problem with devastating consequences in critically ill children¹. Previous prospective pediatric translational work demonstrated that AKI occurs in 10-40% of children admitted to a pediatric intensive care (PICU)² and that Stage 2 or 3 AKI (severe AKI, or sAKI) is associated with morbidity and mortality in critically ill children^2-5. Currently, only supportive measures such as renal replacement therapy (RRT) are offered to critically ill patients with AKI. Debate still exists about RRT initiation timing, as clinicians have not had reliable tools to predict which patients will develop AKI. Lack of reliable sAKI risk assessment represented a significant gap for optimal RRT timing for only those patients who need it.

The previous TAKING FOCUS 2 Trial, a single-center POC-AKI study, demonstrated both an 18.9% absolute survival rate improvement and an 11-day LOS reduction among surviving patients in the PICU who received continuous renal replacement therapy (CRRT). The objective of the TARGET (Treatment of AKI Using RAIdar Guided EHR Triage) Trial is to demonstrate comparable results of the single-center TAKING FOCUS 2 Trial to that of Phase 1 Multicenter Real Time POC-AKI ICU Improvement Collaborative.

Design

• Multicenter prospective interventional POC-AKI all-comer triage trial design modelled after TAKING FOCUS 2
• Retrospective baseline benchmarking (Pre-RAI)
• Prospective interventional analyses (Post-RAI)
• 10-15 RAI/NGAL enabled hospital PICU sites selected
• Study participants design data fields in partnership with Cincinnati Children's & Lurie Children's
• Spearhead of the NEXUS Collaborative

Study Group

• RAI & biomarker excludes 90-95% patients not at-risk for AKI: Enrollment enrichment may reduce study sample size, time, and costs⁶ for research or industry-sponsored trials
• Interventional studies not limited to CRRT will have built-in control and treatment cohorts allocated either by center or by enrolled participant
• Virtually unique for pediatric AKI drug and device trials
• Opportunity to calibrate algorithms as RAI becomes more specialized in the future (sepsis, cRAI, etc)
• Multicenter data access can be leveraged for multiple grant applications and funding requests

Infrastructure

• RAIDAR Health offers a cloud-based, RAI Service that provides CCHMC-licensed Clinical Decision Support using the RAI protocol to hospital electronic health record (EHR) systems.
• RAIDAR Health hosts a centralized, real-time, shared repository for TARGET data.

Governance

• Academic outputs governed by the Study Group, not RAIDAR Health
• Study sites led by clinical collaborators, not RAIDAR Health
• Centralized RAIDAR Health hosting enables seamless compilation of data points across unique client EHR's in real-time
• RAIDAR Health services ensures participant data is compiled accurately & consistently across sites
• RAIDAR Health data repository required for participation
• Multicenter data access, usage and publications controlled by the collaborating sites

Interested?

To learn more about participating in TARGET, email us at [email protected].

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1. Kaddourah A, Basu RK, Bagshaw SM, et al. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults. N Engl J Med 2017; 376: 11-20.
2. Akcan-Arikan A, Zappitelli M, Loftis LL, et al. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 2007; 71: 1028-1035.
3. Sutherland SM, Byrnes JJ, Kothari M, et al. AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions. Clin J Am Soc Nephrol 2015; 10: 554-561.
4. Sanchez-Pinto LN, Goldstein SL, Schneider JB, et al. Association Between Progression and Improvement of Acute Kidney Injury and Mortality in Critically Ill Children. Pediatr Crit Care Med 2015; 16: 703-710.
5. Schneider J, Khemani R, Grushkin C, et al. Serum creatinine as stratified in the RIFLE score for acute kidney injury is associated with mortality and length of stay for children in the pediatric intensive care unit. Crit Care Med 2010; 38: 933-939.
6. Kellum JA & Devarajan P. What can we expect from biomarkers for acute kidney injury? Biomark Med. 2014 ; 8(10): 1239-1245.