Prospective Randomized Wait-List Control Trial Of IV Iron Sucrose In Older Anemic Adults With Serum Ferritin Of 20-200ng/Ml

Background Anemia is a common problem in older adults. Approximately one third of anemic adults 65 years and older have unexplained anemia of the elderly (UAE) as no clear cause can be identified. The Partnership for Anemia: Clinical and Translational Trials in the Elderly (PACTTE), an NIH funded consortium to perform interventional trials in this population, conducted a randomized prospective wait-list control study of the value of IV iron sucrose (IS). PACTTE consists of eight clinical sites (seven university based and one community based) and one data coordinating center. We hypothesized that UAE patients (pts) with moderate serum ferritin levels and no bleeding would benefit from iron repletion. Methods Pts 65 years and older with UAE, hemoglobin (Hb) values between 9 g/dL and 11.5 g/dL (in women) and 12.7 g/dL (in men) inclusive, serum ferritin levels between 20 and 200 ng/mL, and negative stool cards for occult blood, were randomized to receive 5 weekly doses of 200 mg of intravenous iron sucrose (Venofer®, Luitpold Pharmaceuticals), either immediately (immediate group) or to watch and wait (wait list group) for a 12 week waiting period. After 12 weeks, the wait-list control received IV Iron. The primary outcome was the difference in change in 6 minute walk test (6MWT) distance, from baseline to week 12 between the two groups. Secondary outcome measures included erythroid response, cognitive function, self-report function (FACT-An), quality of life (SF-36), and frailty (Fried Frailty Index). We targeted enrollment of 84 patients to provide 85% power to detect 50 meters difference in 6MWT distance. Results 43 pts were formally screened and 19 pts enrolled with a mean age of 78.5 years. 9 pts were randomized to the immediate group and 10 to the wait list group. The study was stopped due to poor accrual both related to strict eligibility and problems identifying pts to be screened. Baseline hematologic and demographic characteristics of the immediate and wait-list groups were similar except for a few variables such as lower serum iron (55.3 vs 84.5 mcg/dL, p=0.006) and transferrin saturation (12.4% vs 27.4%, p=0.015) in the immediate group. However, serum ferritin was similar (79 ng/mL in immediate and 53 ng/mL in wait-list, p=0.21). There was no significant difference in the primary outcome: at week 12, the immediate intervention group had a mean increase of 8.05± 55.48 meters on the 6MWT and the wait list group had a mean decline of 11.45±49.46 meters walked (p=0.44). Hb rose 0.39 g/dL ± 0.46 in the immediate intervention group compared to a mean decline of 0.39 ± 0.85 in the wait list group (p=0.026). Anemia symptoms improved by the FACT-An in the immediate group compared to the wait list group (+7.3 ±10.4 vs. -1.3 ±8.2, p=0.03). There were no significant differences in other secondary outcomes. Two patients in the immediate intervention group and 1 patient in the wait list group experienced grade 1 or grade 2 possibly or probably related treatment adverse events. One patient in each group experienced a serious adverse event, considered unlikely to be related to the study drug. Discussion The study was hampered by difficulty in recruitment. Future studies of older adults with UAE likely will require more sites, less stringent eligibility, and methods to screen and stimulate interest among eligible community dwelling subjects and their physicians. Nevertheless, the improvements in symptoms and hemoglobin from IV iron, in this limited sample justify further evaluation of IV iron in UAE with low to normal iron stores if recruitment barriers can be overcome. Disclosures: Off Label Use: IV iron with venofer is off label and given for unexplained anemia with low to normal iron stores.