title: 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).
abstract: 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.
  
  
  CONCLUSIONS
  PREDICT will determine the optimum target Hb for Japanese patients with non-diabetic CKD. (ClinicalTrials.gov No. NCT01581073).
authors.affiliation: Nakayamadera Imai Clinic, 2-8-18 Nakayamadera, Takarazuka, 665-0861, Japan. ADS12069@nifty.com.|Department of Nephrology, Fujita Health University, Toyoake, Japan. ADS12069@nifty.com.
authors.forename: Enyu
authors.initials: E
authors.lastname: Imai
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.affiliation: Fukuoka Red Cross Hospital, Fukuoka, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hirakata
authors.affiliation: Osaka General Hospital, Osaka, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: 2nd Department of Medicine, Niigata University Graduate School of Medicine, Niigata, Japan.
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kono
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakatani
authors.affiliation: Department of Biostatistics, Kyoto University, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Nephrology, Osaka University, Suita, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsubakihara
authors.affiliation: Department of Nephrology, Showa University, Tokyo, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Akizawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D000068256:Darbepoetin alfa / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007564:Japan; D007668:Kidney / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; D000068256:Darbepoetin alfa
keywords: CKD; ESRD; Erythropoietin-stimulating agent; Hemoglobin