HOLISTIC Trial Tests Embedded Pharmacists in Primary Care
The upcoming HOLISTIC trial seeks to determine whether embedding pharmacists in primary care clinics, supported by nephrologists and cardiologists, can improve outcomes for patients with cardiovascular-kidney-metabolic syndrome. The study involves six health systems and will test if coordinated care models can accelerate the delivery of new therapies to high-risk individuals earlier in their disease progression.
Study Design and Participants
Katherine Tuttle, M.D., executive director for research at Providence Inland Northwest Health and a University of Washington professor of medicine, is leading Providence’s participation in the trial. The study involves six health systems: Providence, UCLA Health, UT Southwestern, University of North Carolina, Brigham and Women’s Hospital, and the University of Minnesota. Coordination will occur through the Baim Institute for Clinical Research in Boston.
In the trial, a pharmacist will be embedded with primary care professionals and supported by nephrology and cardiology specialists. These pharmacists will handle much of the medication management, reducing the burden on primary care physicians. Weekly case conferences, similar to tumor boards, will bring specialists together to review patients with diabetes and high-risk chronic kidney disease. These meetings will guide the rapid implementation of four guideline-directed therapies.
Providence will deploy six primary care clinics in the study. Three will continue with standard care, while the other three will integrate pharmacists working weekly with cardiology and nephrology teams. These integrated clinics will conduct case reviews to assess how effectively and quickly therapies are implemented and monitored.
Measuring Success and Policy Implications
The trial’s primary outcomes include whether patients receive guideline-directed medical therapy, the speed of its implementation, and downstream health system metrics such as mortality, hospitalizations, dialysis initiation, and heart disease events. A robust economic analysis will also be conducted to evaluate cost-effectiveness.
The Center for Medicare & Medicaid Innovation (CMMI) is closely monitoring the trial. CMMI’s prior Kidney Care Choices Model, designed for CKD stages 4 and 5, achieved modest results and cost the program $300 million more than expected in 2023. The model focused on traditional therapies like ACE inhibitors and ARBs, which are less effective than newer options now available.
Current therapeutic options for cardiovascular and kidney disease include SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists—drugs with proven kidney and cardiovascular benefits. Early detection and treatment of CKD stage 3 patients (GFR below 60) could reduce kidney failure rates by 55%. CMMI is considering a value-based model centered on early detection and rapid therapy deployment rather than dialysis optimization, though policy changes would be required for implementation.
Tuttle emphasized that success hinges not just on clinical outcomes but on creating a scalable model that improves value-based kidney care. The study, launching in early 2027 and running through 2030, includes a federally qualified health center clinic in Colville alongside main campus sites.
Researcher Background and Career Recognition
Katherine Tuttle’s expertise extends beyond her leadership role in the HOLISTIC trial. She has been recognized with the 2026 Clinical Research Prize and the 2026 Distinguished Service Award from the American Heart Association, highlighting her contributions to cardiovascular and kidney disease research. Her work in the Spokane region focuses on treating patients with chronic conditions that often intersect, providing practical insights for the trial’s real-world application.
Tuttle’s research spans decades, with a significant focus on GLP-1 receptor agonists and their kidney-protective effects independent of their metabolic benefits. Her clinical practice drives the trial’s emphasis on early intervention, ensuring that the study addresses gaps between academic findings and patient care. “I’m a physiologist by trade,” Tuttle explained, emphasizing the importance of translating research into actionable treatment strategies.
Policy Considerations and Rural Healthcare Integration
CMMI’s interest in the HOLISTIC trial reflects a shift toward upstream interventions. The previous Kidney Care Choices Model, focused on dialysis optimization, yielded less than 10% improvement in key metrics and incurred unexpected costs. CMMI now prioritizes models targeting earlier disease stages, where newer therapies like SGLT2 inhibitors and finerenone show greater promise. This approach aligns with Tuttle’s vision of value-based care that emphasizes prevention and rapid treatment deployment.
