Effects of Individualized Anemia Therapy on Hemoglobin Stability: A Randomized Controlled Pilot Trial in Patients on Hemodialysis

Abstract

Key Points:

1. We conducted a randomized controlled pilot trial in patients on hemodialysis using a physiology-based individualized anemia therapy assistance software.

2. Patients in the group receiving erythropoiesis-stimulating agent dose recommendations from the novel software showed improvement in hemoglobin stability and erythropoiesis-stimulating agent utilization.

Background: Anemia is common among patients on hemodialysis. Maintaining stable hemoglobin levels within predefined target levels can be challenging, particularly in patients with frequent hemoglobin fluctuations both above and below the desired targets. We conducted a multicenter, randomized controlled trial comparing our anemia therapy assistance software against a standard population-based anemia treatment protocol. We hypothesized that personalized dosing of erythropoiesis-stimulating agents (ESAs) improves hemoglobin target attainment.

Methods: Ninety-six patients undergoing hemodialysis and receiving methoxy polyethylene glycol-epoetin beta were randomized 1:1 to the intervention group (personalized ESA dose recommendations computed by the software) or the standard-of-care group for 26 weeks. The therapy assistance software combined a physiology-based mathematical model and a model predictive controller designed to stabilize hemoglobin levels within a tight target range (10–11 g/dl). The primary outcome measure was the percentage of hemoglobin measurements within the target. Secondary outcome measures included measures of hemoglobin variability and ESA utilization.

Results: The intervention group showed an improved median percentage of hemoglobin measurements within target at 47% (interquartile range, 39–58), with a 10% point median difference between the two groups (95% confidence interval, 3 to 16; P = 0.008). The odds ratio of being within the hemoglobin target in the standard-of-care group compared with the group receiving the personalized ESA recommendations was 0.68 (95% confidence interval, 0.51 to 0.92). The variability of hemoglobin levels decreased in the intervention group, with the percentage of patients experiencing fluctuating hemoglobin levels being 45% versus 82% in the standard-of-care group. ESA usage was reduced by approximately 25% in the intervention group.

Conclusions: Our results demonstrated an improved hemoglobin target attainment and variability by using personalized ESA recommendations using the physiology-based anemia therapy assistance software.

Clinical Trial registration number:: NCT04360902.

Keywords: anemia; erythropoietin; hemodialysis; randomized controlled trials.

Graphical abstract

Figure 1

Summary of the study populations. Study analysis was performed on the analytical cohort (i.e., patients who contributed at least 30 days of data during the study period). The median follow-up period was 26 weeks, with no variability within the IQR, in both groups.

Figure 2

Primary outcome measure, percentage of hemoglobin within target, improved in the intervention group (analysis cohort). Triangles indicate the mean and white lines the median values. The boxes show the quartiles of the data and whiskers extend to show the rest of the distribution, except for values outside 1.5 times of the IQR that are depicted as outliers. IQR, interquartile range.

Figure 3

Secondary outcome measures related to hemoglobin variability improved in the intervention group (completed study population). Triangles indicate the mean and white lines the median values. The boxes show the quartiles of the data and whiskers extend to show the rest of the distribution, except for values outside 1.5 times of the IQR that are depicted as outliers. (A) Progression of the mean monthly hemoglobin levels per patient throughout the study. The blue shaded area indicates the hemoglobin target of 10–11 g/dl. (B and C) Hemoglobin SD and hemoglobin distance to the target for each patient during the study period. Four outliers in (C) are shown by arrows and numerical values.

Figure 4

Secondary outcome measure: Monthly ESA doses were consistently lower in the intervention group compared with the standard-of-care group (completed study population). Triangles indicate the mean and white lines the median values. The boxes show the quartiles of the data and whiskers extend to show the rest of the distribution, except for values outside 1.5 times of the IQR that are depicted as outliers. ESA, erythropoiesis-stimulating agent.