Does a higher or lower target for phosphate control offer the best balance of benefits and risks in patients receiving maintenance hemodialysis? This important question remains unanswered, after the HiLo research team reported on the challenges that led to early termination of their innovative pragmatic clinical trial.
The article was published online ahead of print in the Journal of the American Society of Nephrology.
HiLo, an NIH Collaboratory Trial, compared the effects of higher vs lower serum phosphate targets on all-cause mortality and all-cause hospitalization in patients undergoing maintenance hemodialysis. Evidence from randomized clinical trials to inform the optimal phosphate target is lacking.
Patients in the low phosphate target group received the standard clinical approaches to phosphate management. For patients in the high phosphate target group, clinicians and dietitians withdrew phosphate binders and relaxed dietary restrictions if the phosphate level remained below target.
HiLo began as a cluster randomized trial with randomization at the dialysis facility level. Nearly 2 years into the trial, an imbalance in baseline serum phosphate between the study groups raised concern about biased recruitment. The study team transitioned to patient-level randomization before eventually stopping the trial early due to insufficient enrollment and inadequate phosphate separation between groups. As a result, the study team was unable to detect a difference in the primary outcome or to make inferences about secondary outcomes.
Although HiLo was stopped early, the trial’s design had several pragmatic features that point the way for future trials. The trial used no onsite research staff, instead engaging sites’ clinical staff to deliver the intervention as part of routine care. The study team monitored monthly laboratory data remotely and provided real-time feedback to the sites. All laboratory and outcome data were collected in the context of clinical care.
Disruptions from the COVID-19 pandemic, complications related to the trial’s original cluster randomized design, and other challenges also offer lessons for future studies.
HiLo was supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases.
The NIH Pragmatic Trials Collaboratory is pleased to announce that the IMPACt-LBP NIH Collaboratory Trial received approval this month to transition from the planning phase to the implementation phase. This pragmatic clinical trial embedded in healthcare systems is studying implementation of guideline-based care for low back pain, a leading cause of ambulatory care visits in the United States.