The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration

Abstract

Significance Statement Routine incorporation of pragmatic trials into clinical care delivery has potential to generate answers to important questions, such as optimal approaches for fundamental components of maintenance hemodialysis. The Time to Reduce Mortality in ESRD (TiME) trial was a large pragmatic trial demonstration project designed to determine if a hemodialysis session duration longer than many patients in the United States currently receive improves clinical outcomes. Although the trial accomplished many of its demonstration project objectives, including rapid enrollment of >7000 patients, use of an opt-out consent approach, and complete reliance on clinically acquired data, uptake of the intervention was insufficient to determine whether longer sessions improve outcomes. Embedding trials into hemodialysis clinical care will require more effective strategies for engaging clinical personnel and patients. Background Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established. Methods To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients. Results The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care. Conclusions Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.