The investigators of HiLo, an NIH Collaboratory Demonstration Project, have received approval to move from the planning phase to the implementation phase of their study. Congratulations to Dr. Myles Wolf and the HiLo study team for their excellent work!
HiLo (Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis) is designed to answer the question of what is the optimal level of serum phosphate for patients with end-stage renal disease (ESRD) who are undergoing hemodialysis. In an effort to improve clinical outcomes, current practice guidelines advocate aggressive treatment of high blood phosphate to near normal levels using dietary phosphate binders and restrictive diets. Yet, the optimal phosphate target remains unknown, and potential harms of aggressive treatment have not been definitively identified. HiLo is the first formal clinical research study to evaluate this important question. The study team is planning the first wave of site activations with the goal of beginning enrollment at 10 dialysis centers in the Raleigh-Durham area in October or November.
We recently asked Dr. Wolf to reflect on the transition of the HiLo trial.
Were there any surprises during the study’s planning phase?
How much work was required to plan a large pragmatic trial! Fortunately, we have a superb team of investigators and study staff who are deeply invested in the trial, deep expertise at the Duke Clinical Research Institute, full engagement of our partners at DaVita and the University of Utah, invaluable insight from our Patient Ambassadors from the American Association of Kidney Patients, and unwavering support from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the NIH Collaboratory.
What is an example of a challenge that you were able to overcome with the help of a Core group?
The Ethics and Regulatory Core helped us work through unique challenges related to obtaining individual-level informed consent in a cluster-randomized trial. The Biostatistics and Study Design Core and a number of outside statistical consultants helped us identify a novel solution for designing and analyzing a primary outcome of the trial that best aligns with the study’s clinical goal.
“We hope that the experience we gained from HiLo related to application of novel methods for pragmatic trials will stimulate further innovation and enhance the design of future studies in our field, ultimately for the benefit of kidney patients.” – Dr. Myles Wolf, PI of HiLo
What other key challenges have you faced?
We learned from the Ambassadors on our Patients Advisory Group about how important it will be to convince dialysis facility staff and patients that it is justified and important for the study to reevaluate what has been dogma in ESRD treatment: that serum phosphate must be lowered aggressively. We have had to grapple with how to deploy an electronic process to obtain informed consent remotely—a first in U.S. dialysis studies—given that we will not have on-site study coordinators in the participating dialysis facilities. We also had to develop, refine, and defend our use of a newer statistical approach to HiLo’s primary hierarchical composite outcome of all-cause mortality and all-cause hospitalizations. The approach, which is gaining traction in other areas, has not been used in large-scale trials in nephrology. While the process of preparing for this trial was long and required substantial hard work from a large team of investigators and study staff, we hope that the experience we gained from HiLo related to application of novel methods for pragmatic trials will stimulate further innovation and enhance the design of future studies in our field, ultimately for the benefit of kidney patients.
What words of advice do you have for investigators conducting their first embedded PCT?
Get to know the people—patients and professionals—who need to be invested and will be affected by your study and its outcomes. Understand their interests and concerns even if it goes against what you think you know. These early conversations will help identify hurdles at a time when they can be readily addressed and the study enhanced. Be patient and be prepared to work, and work some more. And ask for more money … pragmatic plus more resources is still pragmatic!
Additional details about the study are on the HiLo website.
NIH Collaboratory Demonstration Projects begin with a 1-year, milestone-driven planning phase. Projects become eligible to move to the implementation phase after an administrative review of progress toward scientific milestones and feasibility requirements. Throughout the process, the project team interacts with the Core Working Groups and investigators from the other Demonstration Projects.
HiLo is supported within the NIH Collaboratory by a cooperative agreement from the NIDDK and receives logistical and technical support from the NIH Collaboratory Coordinating Center. Read more about HiLo in the Living Textbook, and learn more about the NIH Collaboratory Demonstration Projects.