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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)

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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 m2. The primary outcome is a composite renal endpoint (starting chronic dialysis, transplantation, eGFR 6 mL/min/1.73 m2 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).

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Conflict of interest

Employment/Leadership position/Advisory role: Tadao Akizawa (Kyowa Hakko Kirin, Japan Tabaco, Astellas, Nipro), Consultancies: Masaomi Nangaku (Kyowa Hakko Kirin, Chugai), Manuscript fee: Tadao Akizawa (Kyowa Hakko Kirin, Astellas), Honoraria: Enyu Imai (Daiichi Sankyo, Dainippon Sumitomo, Kyowa Hakko Kirin, Chugai, MSD, Sanwa Kagaku), Terumasa Hayashi (Kyowa Hakko Kirin, Chugai), Masaomi Nangaku (Kyowa Hakko Kirin, Chugai), Hideki Hirakata (Chugai, Kyowa Hakko Kirin, Japan Tabaco, Bayer, Torii, Astellas), Ichiei Narita (Mochida, Novartis, Daiichi Sankyo, MSD, Mitsubishi Tanabe), Yoshihara Tsubakihara (Chugai, Kyowa Hakko Kirin, Mitsubishi Tanabe), Tadao Akizawa (Chugai, Bayer, Kyowa Hakko Kirin). Grants received: Shoichi Maruyama (Kyowa Hakko Kirin, Otsuka, Dainippon Sumitomo, Mochida), Masaomi Nangaku (Kyowa Hakko Kirin, Chugai), Ichiei Narita (KUREHA, Chugai, Astellas, Kyowa Hakko Kirin, Genzyme Japan, Daiichi Sankyo, Takeda). Endowed departments by commercial entities; Yoshiharu Tsubakihara (Chugai, Baxter).

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Authors and Affiliations

  1. Nakayamadera Imai Clinic, 2-8-18 Nakayamadera, Takarazuka, 665-0861, Japan

    Enyu Imai

  2. Department of Nephrology, Fujita Health University, Toyoake, Japan

    Enyu Imai

  3. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Shoichi Maruyama

  4. Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan

    Masaomi Nangaku

  5. Fukuoka Red Cross Hospital, Fukuoka, Japan

    Hideki Hirakata

  6. Osaka General Hospital, Osaka, Japan

    Terumasa Hayashi

  7. 2nd Department of Medicine, Niigata University Graduate School of Medicine, Niigata, Japan

    Ichiei Narita

  8. Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan

    Hideki Kono & Eiji Nakatani

  9. Department of Biostatistics, Kyoto University, Kyoto, Japan

    Satoshi Morita

  10. Department of Nephrology, Osaka University, Suita, Japan

    Yoshiharu Tsubakihara

  11. Department of Nephrology, Showa University, Tokyo, Japan

    Tadao Akizawa

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  1. Enyu Imai
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  11. Tadao Akizawa
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Correspondence to Enyu Imai.

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Imai, E., Maruyama, S., Nangaku, M. et al. 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). Clin Exp Nephrol 20, 71–76 (2016). https://doi.org/10.1007/s10157-015-1133-z

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  • DOI: https://doi.org/10.1007/s10157-015-1133-z

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