Rationale and study design of a randomized controlled trial to assess the effects of maintaining hemoglobin levels using darbepoetin alfa on prevention of development of end-stage kidney disease in non-diabetic CKD patients (PREDICT Trial).

Background: Anemia associated with high mortality is a common complication of chronic kidney disease (CKD). Target hemoglobin (Hb) levels for CKD treatment remain controversial: Recent guidelines recommend a maximum of 13 g/dL to avoid increased risk of CVD. However, some smaller studies show slower progression of renal function loss with high Hb targets. Recently, darbepoetin alfa targeting Hb 11-13 g/dL was reported to improve renal composite outcome of Japanese patients compared with a low Hb group maintained at 9.0-11.0 g/dL using epoetin alfa (HR 0.66; 95% CI 0.47-0.93). The high Hb group showed significant reduction of left ventricular mass index and improved quality of life. Sub-analysis revealed greater beneficial effects in non-diabetic stage 5 CKD patients. This randomized controlled trial, PREDICT, aims to confirm the impact of targeting Hb levels of 11-13 g/dL using darbepoetin alfa with reference to a low Hb target of 9-11 g/dL.

Methods: We calculated the number of subjects (N = 440) necessary to detect a statistically significant level of α = 0.05 (two-sided) and statistical power of 80% for a minimum follow-up period of 2 years on the basis of a previous study.

Results: The study enrolled 498 non-diabetic Japanese patients with eGFR 8-20 mL/min/1.73 m(2). The primary outcome is a composite renal endpoint (starting chronic dialysis, transplantation, eGFR 6 mL/min/1.73 m(2) or less, 50% decrease in eGFR). Average follow-up period is 2 years and the study ends in 2016.

Conclusion: PREDICT will determine the optimum target Hb for Japanese patients with non-diabetic CKD. (ClinicalTrials.gov No. NCT01581073).