Correction of Anemia in the Frail Elderly (CAFÉ): Results of a Randomized, Double-Blind, Placebo-Controlled Study with Darbepoetin Alfa in Elderly Patients with Chronic Unexplained Anemia

To evaluate the effect of darbepoetin alfa treatment on hemoglobin (Hb) levels in frail, community dwelling elderly patients with chronic unexplained anemia and its correlation with the presence of comorbidities, serum baseline erythropoietin concentrations and renal function.

A 24 weeks, prospective, randomized (1:1), double-blind, placebo-controlled clinical trial.

Eighty community-dwelling, consenting pre-frail or frail (Hopkins Frailty Index score 1 to 3) patients 70 years or older with chronic anemia (Hb <11. 5 g/dL).

Subcutaneous darbepoetin alfa or placebo weekly for 24 weeks with a 22 week open-label extension. Initial dose 60 μg every other week (bi-weekly).

Hemoglobin, Erythropoietin serum levels, estimated glomerular filtration rate, Charlson Comorbidity Index and Age Adjusted Comorbidity Index scores.

80 subjects were enrolled, and complete data was analyzed. Of those enrolled, most were White (86. 25%) and male (58. 75%) and had a low comorbidity score, and a mean age ± standard deviation 81. 34 ± 6. 34. Mean baseline Hb was 10. 93 ± 0. 57 g/dL (9. 1–11. 9). Erythropoietin baseline levels (mU/mL) for placebo arm were 21. 4 ± 15 and 17. 6 ± 12. 4 for treatment arm. Estimated Glomerular filtration rates at baseline, mL/min per 1. 73m2 were 58. 7 ± 22. 4 and 50. 5 ± 17. 7 for placebo and treatment arms, respectively. During the observation period, there was a significantly greater hematopoietic response (mean 1. 13 ± 0. 59 g/dL) in the participants treated with darbepoetin alfa than in those receiving placebo (0. 3 ± 0. 18 g/dL). All participants (100%) responded to darbepoetin alfa treatment by week 8, attaining the target Hb level of 12 g/dL and maintaining those levels throughout the observation period. The average bi-weekly dose of darbepoetin alfa required to achieve the hemoglobin goal of 12 g/dL by week 8 was 63. 1 ± 3. 5 μg. After the eight week, 77% required less than 40. 46 ± 5. 4/week, and 23 patients (58. 9%) were maintained on weekly average dosages of less than 35 μg/week. The mean bi-weekly dose of darbepoetin alfa during the 24-week observation period was 74. 7 ± 12. 4 μg subcutaneously. The calculated average weekly dose of darbepoetin alfa needed to increase the hemoglobin levels by 1 g/dL was 40. 63μg/Hb/wk. Among the participants receiving placebo, only 3 out of 41 (7. 31%) patients had levels of Hb 12 g/dL or greater at end of the study (week 24) (P 0. 00006). This response was maintained and more significant among patients with lower age-adjusted comorbidity scores (<9) irrespective of gender, renal function and baseline erythropoietin levels. No significant differences were found between treatment and placebo on high comorbidity scores (≥9). Darbepoetin alfa was well tolerated and no major adverse events were reported in this group of patients with Hb target level of 12 g/dL.

In this trial involving predominantly older white community dwelling patients with anemia, a direct relationship existed between increases in Hb during darbepoetin alfa therapy, this finding being more evident in the groups with lower age-adjusted comorbidity scores. Relatively lower dosages of darbepoetin alfa were required to attain a durable Hb response, with a good safety profile.

Off Label Use: To evaluate the effect of darbepoetin alfa treatment on hemoglobin (Hb) levels in frail, community dwelling elderly patients with chronic unexplained anemia and its correlation with the presence of comorbidities, serum baseline erythropoietin concentrations and renal function.