Ashish K. Khanna, MD,MS, FASA, FCCM a professor of Anesthesiology in the section on Critical Care Medicine at Wake Forest University School of Medicine, received the 2024-2025 Science of Translation Pilot Recipients award for his project ‘Precision-Based Renin Assessment in Septic Shock Outcomes.’ As a senior investigator, he applied to the Wake Forest Clinical and Translational Science Institute (CTSI) Pilot Program to obtain preliminary data for future grant applications. The program's focus on collaborative research networks matched his research goals, providing an excellent platform for scientific advancements.
Dr. Khanna’s current project focuses on understanding the dysfunction within the renin-angiotensin-aldosterone system (RAAS) in septic shock. Conducted as a prospective study, the research involves enrolling adult patients with septic shock across multiple sites, including the main campus ER and ICU in Winston-Salem, North Carolina as well as facilities at High Point and Charlotte. The goal is to identify a set of RAAS biomarkers that can most precisely predict patient outcomes and potentially guide early therapeutic interventions, ultimately improving care for those suffering from septic shock.
The CTSI Pilot Program has provided invaluable assistance through funding that enables complex data collection and advanced biomarker analysis. Additionally, a supplement from the Center for Artificial Intelligence Research (CAIR) has enhanced the research capabilities. The team has facilitated connections with mentors and advisors at each stage of research work, including regular check-ins to monitor the progress in the enrollment of their prospective study. The CTSI team has been an excellent resource for advanced modeling, clinical trial design, and data analytics.
This research initiative has successfully fostered collaboration across multiple sites. At the Winston campus, substantial support has been provided by the Hypertension Center, under the direction of Dr. Mark Chappell, (co-PI) an authority on the RAAS. The project has been further reinforced through collaborations with the Medical ICU team, led by Dr. Clark Files, and the High Point Medical Center ICU, where Dr. Khanna and his clinical colleagues serve. Contributions from Dr. Lane Smith and his team at Atrium Health Charlotte included screening and co-enrollment of patients and transportation of biomarker samples for analysis at the Hypertension Center at the Biotech Place in Winston-Salem. Additionally, early patient screening efforts were supported by Dr. Simon Mahler and his ER team at the Winston campus. Christopher L. Schaich, PhD, assistant professor with the Hypertension Center, is providing expertise with analytics and statistical modelling.
This coordinated effort is managed by research coordinators, Darija Ward, MICU, and laboratory technicians, Kendra Wright, Hypertension Center, Chappell lab, from various departments and is spearheaded by the anesthesiology critical care research team, Tanmay Sura, Brandon Reeves, and Lynnette Harris, at the main campus in Winston-Salem. The initiative encompasses a collective effort among numerous providers and support staff. Efficient communication across research sites has been facilitated through Electronic Health Records (EHR) systems. Research coordinators from the ER and ICU at the three participating hospitals employ EHR to screen patients and coordinate logistics. Though still undergoing refinement, this system has enhanced efficiency and yielded valuable insights for optimizing future clinical trials.
Beyond fostering collaboration, the CTSI Pilot Program has laid the groundwork for larger clinical trials and serves as a foundation for future research initiatives, including the Advocate Health National Center for Clinical Trials (NCCT). Dr. Khanna states, “For me personally, I am honored and thrilled to be working with my colleagues who see the same clinical problems in patients with septic shock and share common ideologies of research. And that I get to work with Mark Chappell, who has pioneered research with the RAAS and has taught me so much in the process, is the perfect icing on the cake. In 2017, I led and published a significant clinical trial of Angiotensin II, an exogenous synthetic vasopressor that modulates the RAAS. Returning to reexamine the mechanics of the RAAS with Mark and his expert team has been exceptionally rewarding. Serendipity, reverse causation, inspiration and gratitude all in one!”
Dr. Khanna’s research data will be utilized to establish groundwork for a randomized trial of therapeutic interventions in septic shock, incorporating an understanding of RAAS dysfunction mechanisms. A portion of this work has already been submitted to the NIH as an R01 and has received a fundable score. Another segment of this effort will extend our trial to a larger population. Dr. Khanna emphasizes, “Ultimately, we hope to innovate and bring RAAS biomarker analysis to the bedside and use it in a real-world patient population to guide interventions (such as specific vasopressor choices) and predict outcomes.” This initiative represents another step towards achieving effective precision medicine in critical care practice.
Encouraging Other Researchers to Apply
When asked if he would recommend other researchers to apply for the CTSI Pilot Program, Dr. Khanna enthusiastically stated, “Most certainly! And in fact, I am working and now expanding the scope of our work with colleagues in cardiac surgery and cardiac anesthesia who will be applying under my mentorship this year! This is the perfect steppingstone to necessary data needed for larger investigations, the peer review process is robust, feedback is timely and useful and shared with investigators and is a great opportunity to understand and utilize CTSI resources and meet the CTSI team and likeminded investigators across the enterprise.”If you are interested in collaborating with the Wake Forest CTSI, please review and request our services here. If you are considering our pilot program and wish to apply for funding, please find the details here.