- Open Access
Vitamin D receptor activator and prevention of cardiovascular events in hemodialysis patients—rationale and design of the Japan Dialysis Active Vitamin D (J-DAVID) trial
Renal Replacement Therapyvolume 2, Article number: 19 (2016)
Activation of vitamin D is severely impaired in patients with advanced stages of chronic kidney disease, particularly those on hemodialysis. Observational studies have shown that the use of vitamin D receptor activators (VDRAs) is associated with lower risk of death from all-cause and cardiovascular disease (CVD) in dialysis populations regardless of serum parathyroid hormone (PTH) level. So far, however, there is no prospective trial to evaluate the effect of VDRAs administration on CVD prevention in hemodialysis patients.
The Japan Dialysis Active Vitamin D (J-DAVID) trial is a multi-center study with a prospective randomized open-label blinded endpoint (PROBE) design. The subjects are maintenance hemodialysis patients whose serum calcium is ≤10.0 mg/dL, phosphate is ≤6.0 mg/dL, and intact PTH is ≤180 pg/mL without taking any VDRA. The subjects (target number is 972) are randomized to one of the two treatment arms: treatment with oral alfacalcidol or treatment without using any VDRA and followed up for 48 months. The primary outcome is the composite of fatal and nonfatal cardiovascular events (myocardial infarction, heart failure requiring hospitalization, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death, coronary revascularization, and leg artery revascularization). The secondary outcome is all-cause death. The primary analysis will be the intention-to-treat analysis of the primary endpoint.
Between July 2008 and January 2011, a total of 976 participants were randomized. The final results are expected in the second half of 2016.
The J-DAVID trial will provide valuable information whether or not administration of VDRA reduces the risk of CVD in hemodialysis patients.
Hemodialysis patients are at an extremely elevated risk of death from all-cause and cardiovascular disease (CVD) in Western countries [1, 2] and in Japan  as well. The excess risk may be attributable to impairment in traditional  and nontraditional risk factors associated with chronic kidney disease (CKD)  such as insulin resistance , inflammation , protein-energy wasting , and CKD-mineral bone disorder (CKD-MBD) .
CKD-MBD is a systemic disorder in which abnormalities in phosphate and calcium metabolism are causatively involved not only in bone disease but also in vascular calcification and poor clinical outcomes in patients with CKD . Patients with reduced kidney function show phosphate retention, increased fibroblast growth factor 23 (FGF23), impaired activation of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvatiamin D (1,25(OH)2D), and secondary hyperparathyroidism . Observational cohort studies have revealed the independent risk factors of mortality including elevated levels of serum phosphate, calcium, and intact parathyroid hormone (PTH) in hemodialysis patients in Western countries  and also in Japan [11, 12]. Furthermore, lower serum levels of 25(OH)D  and 1,25(OH)2D  and higher FGF23  levels are reported to be predictive of all-cause mortality in dialysis patients.
In addition to these abnormalities in laboratory tests, the use of medications for CKD-MBD is known to be associated with clinical outcomes of patients with CKD. The use of activated vitamin D sterols, or vitamin D receptor activators (VDRAs), was reported to be associated with lower risk of all-cause mortality [16–18], CVD-related mortality [19, 20], and incident CVD  in hemodialysis patients. Many, but not all , studies reported such associations as previously reviewed . The hazard ratios of VDRA use versus no use for all-cause mortality were reported in the range between 0.55 and 0.75. In stratified analysis of a large cohort , the lower risk of mortality in VDRA users was significant regardless of serum levels of phosphate and calcium and intact PTH levels.
Although these observational studies suggest the potential benefit of VDRA, a controversy still exists on the overall benefit of treatment with VDRA in dialysis patients. Activation of VDR may increase the risk of CVD and mortality by increasing serum levels of calcium and phosphate, which could promote vascular calcification. Also, by increasing serum FGF23 production , a novel factor potentially promoting left ventricular hypertrophy  and a predictor of congestive heart failure (CHF)  and mortality , the use of VDRA may increase the risk of myocardial remodeling and CHF. On the contrary, VDRAs are shown to have potentially beneficial non-mineral actions  such as suppression of the renin-angiotensin system , modulation of immune functions , anti-inflammatory effects , and anti-atherosclerotic effects  on vascular cells. VDRA inhibits cardiac hypertrophy in experimental animals . In addition, VDRA was reported to increase proteins potentially protective against arterial calcification [32, 33], including serum fetuin A  and klotho expressed in arterial wall . Based on these findings, use of VDRA may suppress cardiac hypertrophy, atherosclerosis, arterial calcification, risk of CHF, atherosclerotic CVD, and mortality in patients with CKD. So far, however, no randomized controlled trials (RCTs) have been performed in hemodialysis patients to examine the possible effects of VDRA on risk of CVD or mortality.
We designed an RCT, the Japan Dialysis Active Vitamin D (J-DAVID) trial, to test a hypothesis that treatment with VDRA reduces the risk of CVD events in hemodialysis patients.
The J-DAVID trial is an RCT with a prospective randomized open-label blinded endpoint (PROBE) design. Eligible patients were randomly allocated to one of the two treatment arms: treatment with oral alfacalcidol (1α-hydroxycholecalciferol) or treatment without any VDRA. The follow-up period was 48 months (Fig. 1).
The target population of this study was maintenance hemodialysis patients whose serum calcium was ≤10.0 mg/dL, phosphate was ≤6.0 mg/dL, and intact PTH was ≤180 pg/mL without taking any VDRA at screening. These values derived from the 2006 version of the clinical practice guideline by the Japanese Society for Dialysis Therapy (JSDT) . Eligibility criteria are shown in Table 1.
Screening and enrollment
Eligible patients were screened at 207 study sites in 27 out of 47 prefectures in Japan (Fig. 2). The registration forms were sent by FAX to the Data Center at Osaka City University for registration and randomization. The registration codes and the assigned treatment groups were sent back by FAX to the attending physician within two working days.
Randomization was performed at a 1:1 ratio using a computer-generated random sequence with a block randomization method stratification by age (<65 years, ≥ 65 years), sex, years on dialysis (<5 years, ≥5 years), underlying renal disease (diabetic nephropathy, others), and prior CVD (with, without). Region of dialysis centers was also considered in randomization because of possible regional disparities in life style, clinical practice patterns, and risk of CVD.
Intervention and control treatment
The participants in the intervention arm were assigned to treatment with oral alfacalcidol at a starting dosage of 0.5 μg per day, which derived from our previous cohort study . The participants in the control arm were assigned to treatment without any VDRA. Except VDRAs, all participants were eligible to receive any other medications for standard medical care including phosphate binders and cinacalcet.
The clinical practice guidelines published by JSDT were the guide for treatment of CKD-MBD in hemodialysis patients. The 2006 version of the guideline  was initially used when the enrollment for J-DAVID was started in 2008. After its revision in 2012 , the revised version was used. Both versions of guideline recommended the same target ranges for serum phosphate and corrected calcium concentrations to be between 3.5 and 6.0 mg/dL and between 8.4 and 10.0 mg/dL, respectively. Regarding intact PTH level, the 2006 version suggested the target range between 60 and 180 pg/mL, whereas the 2012 version suggested the range between 60 and 240 pg/mL with a recommendation that control of serum phosphorus and calcium levels be achieved prior to PTH.
The participants in the intervention arm were asked to avoid other VDRA preparations than oral alfacalcidol, but they were allowed to receive one if clinically needed. We defined the “drop-out” from the assigned treatment at the time when alfacalcidol was not taken continuously for more than 12 weeks in the intervention arm. The participants in the control arm were asked to avoid alfacalcidol and any preparations of VDRA, but they were allowed to receive one if clinically needed. The “drop-out” from the assigned treatment was defined at the time when treatment with any VDRA was done continuously for more than 12 weeks in the control arm. Participants who “dropped-out” from the assigned treatment were followed up until the end of the planned period for the intervention-to-treat (ITT) analysis.
Outcomes and outcome adjudication
The primary outcome was defined as the composite of (1) fatal and nonfatal CVD events (acute myocardial infarction, congestive heart failure, stroke, aortic dissection/rupture, amputation of ischemic limb, and cardiac sudden death), (2) coronary intervention (plain old balloon angioplasty, stenting) or bypass grafting, (3) lower limb artery intervention (plain old balloon angioplasty, stenting) or bypass grafting. The definitions of the individual CVD events are listed in Table 2. The secondary outcome was defined as all-cause death. All these outcomes are being prospectively adjudicated by the Event Evaluation Committee with the assigned treatment of each case being masked to the Committee.
All serious adverse events (SAEs) and laboratory data are reported for safety. SAEs are defined as any undesirable experience during the study when the patient outcome is (1) death, (2) life-threatening, (3) hospitalization (initial or prolonged), (4) disability or permanent damage, (5) congenital anomaly/birth defect, or (6) other important medical events. SAEs are being prospectively adjudicated by the Event Evaluation Committee with the assigned treatment of each case being masked to the Committee. The laboratory data include serum intact PTH, calcium, phosphate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and others.
Source data verification
We planned to perform source data verification (SDV) by a sampling SDV. The minimum number of the extracted patients (31) was determined by √N, where N = 976. Sampling of participants was done by two steps using a computer-generated sequence. First, dialysis facilities were extracted, and then participants were sampled from the participants in the facility. In this study, SDV was only performed regarding the primary and secondary outcomes.
The Steering Committee, which was lead by three academic investigators, nominated the members of the Executive Committee which promoted this study by organizing the research group (J-DAVID Research Group) comprised of dialysis facilities. Independent of the Steering Committee, the Executive Committee, and the J-DAVID Research Group, the J-DAVID study had the Data Center, the Event Evaluation Committee, the Statistics Team, the Independent Data Monitoring Committee, and the Audit Team. These contributors to the J-DAVID study are collectively called “J-DAVID Investigators” (Appendix).
Sample size and power calculation
Assuming (1) that 28 % of participants in the control arm experience the primary outcome during the 4-year period, (2) that the risk is reduced by 30 % in the intervention arm, and (3) that 5 % of participants are lost to follow-up, the trial requires a minimum of 972 participants to detect difference in proportion of the primary endpoint between the two arms with 80 % power (ß level of 0.2) and α level of 0.05.
We assumed the rate of the primary outcome based on a cohort study of 45,390 prevalent Japanese hemodialysis patients without history of prior myocardial infarction or stroke at baseline . The incidence rates of myocardial infarction, cerebral infarction, and cerebral bleeding during the 1-year follow-up (2004) were 1.43, 2.53, and 0.21 per 100 patient-year, respectively (4.17 in total) . Some patients were expected to have avoided such clinical events by timely interventions. In addition, the incidence of these CVD events and interventions are expected to be much higher in patients with prior CVD than those without prior CVD. Thus, we assumed the rate of the primary outcome to be 7–9 % annually.
We assumed 30 % of the relative risk reduction based on previous observational cohort studies of prevalent hemodialysis patients. The hazard ratio of oral VDRA use versus nonuse for CVD mortality was reported to be 0.377 (95 % confidence interval 0.246–0.578) by a study from Japan  and 0.59 (95 % confidence interval 0.40–0.88) by a study in Latin American countries .
Interim analysis was planned to be performed once by the Independent Data Monitoring Committee upon request by the Committee with a Haybittel-Peto method. On the interim analysis, 0.0001 of α is to be spent, and the final α is to be reduced to 0.0499 to maintain the study-wise α level of 0.05.
We defined three populations for analysis: full analysis set (FAS), per-protocol set (PPS), and modified per-protocol set (modified PPS). (1) The FAS consists of all participants who were randomized and participants who “dropped-out” from the assigned treatment are not censored at the time of “drop-out.” (2) The PPS consists of all participants who were randomized, but participants are censored at the time of “drop-out” from the assigned treatment. (3) The modified PPS consists of all participants who were randomized, and participants are censored as follows: In the control arm, participants are censored at the time of “drop-out” from the assigned treatment. In the intervention arm, participants who are censored at the time of “drop-out” from the assigned treatment with oral alfacalcidol, if no VDRA is given in place of alfacalcidol. Participants in the intervention arm are not censored at the time of “drop-out” from the assigned treatment with oral alfacalcidol, if the participants are kept treated with an oral or intravenous VDRA other than alfacalcidol, but such patients are censored at the time when any VDRA is not given continuously for more than 12 weeks.
The primary analysis will be performed using time after randomization to the occurrence of the primary composite outcome with the FAS based on the Kaplan-Meier method with log-rank test. Hazard ratio and confidence interval will be calculated with an unadjusted Cox proportional hazards model for the primary composite outcome and its breakdown. The key secondary analysis will be done with time after randomization to the secondary outcome (all-cause death) with the FAS based on the same methods as above. Additionally, the primary and secondary outcomes will be analyzed with the PPS and the modified PPS as sensitivity analysis.
Participant recruitment and baseline characteristics
Recruitment of participants began in July 2008 and completed in January 2011. Eligibility was assessed in 1289 patients, and 976 patients from 108 dialysis facilities were enrolled and randomized. Table 3 gives the baseline characteristics of the total participants.
The J-DAVID study was originally designed to test a hypothesis that treatment with VDRA reduces the risk of CVD events as the primary endpoint and/or all-cause mortality as the secondary endpoint in hemodialysis patients. This hypothesis was based on the observational clinical studies and experimental studies reporting potential benefit of VDRAs.
After the enrollment for J-DAVID study was started in 2008, there have been two published RCTs regarding the use of VDRA and CVD in patients with CKD. The first one was the PRIMO study  and the second one was the OPERA study , both of which examined the effects of oral paricalcitol on left ventricular hypertrophy as determined by cardiac magnetic resonance imaging among predialysis patients with CKD. These two studies showed no significant effect of treatment with paricalcitol on the primary endpoint. Of note, however, CVD events were fewer in the paricalcitol group than the placebo group in the PRIMO study, and the number of hospitalization was fewer in the paricalcitol group than the placebo group in the OPERA study. These results are an additional support for the hypothesis of the J-DAVID study. So far, no RCT has been published that examined the VDRA’s effect on CVD events or mortality in hemodialysis patients as well as in predialysis patients with CKD.
The use or nonuse of VDRA affects serum levels of phosphate, calcium, and intact PTH. Therefore, in order to maintain the key laboratory data within the target ranges, dietary therapy, and other medications would be changed over time after starting the assigned treatment. As compared with the participants in the control arm, the participants in the intervention arm may have higher levels of serum calcium and phosphate, and lower levels of intact PTH level on average, after starting the assigned treatment. More patients in the intervention arm may be treated with non-calcium-containing phosphate binders, whereas more patients in the control arm may be treated with cinacalcet. A meta-analysis showed a lower risk of death was associated with the use of non-calcium containing phosphate binders as compared with calcium containing phosphate binders in patients with CKD . The same observation was made for either sevelamer hydrochloride  or lanthanum carbonate  in the elderly hemodialysis patients. Also, there is a discussion whether or not cinacalcet has cardio-protective actions . Therefore, any effects on the primary and secondary endpoints in the J-DAVID study will not be purely attributable to the effect of alfacalcidol. Rather, this study would clarify whether the VDRA-based treatment is better than the treatment avoiding VDRA in terms of CVD prevention when other medications are available.
The current clinical practice guidelines for the management of CKD-MBD are largely based on observational cohort studies showing the associations of laboratory tests with all-cause mortality. However, the medications used for the control of the laboratory tests may be more important for clinical outcomes than the achieved serum levels of phosphate, calcium, and PTH. According to a recent meta-analysis , there are only weak and imprecise correlations of drug effects on serum levels of phosphate, calcium, and PTH with all-cause and cardiovascular death in patients with CKD, suggesting that the drug’s non-mineral actions favorably affected these clinical endpoints. The same has been suggested also by previous cohort studies in which the use of VDRAs [16–21] or the use of phosphate-binders [21, 46] were associated with a lower risk of all-cause death, CVD death, or incident CVD in dialysis patients, even after adjusted for serum calcium, phosphate, and PTH levels. The J-DAVID study will reveal whether or not the VDRA treatment reduces CVD and/or mortality even when the current target ranges of phosphate, calcium, and intact PTH are respected.
The J-DAVID study will be the first trial providing valuable information whether or not oral VDRA-based treatment reduces the risk of CVD and/or mortality in hemodialysis patients who are treated by respecting the recommended target ranges of serum phosphate, calcium, and intact PTH.
Ethical approval and consent to participate
This study was performed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Clinical Research by the Ministry of Health, Labor and Welfare, Japan (July 30, 2003; December 28, 2004 all amendments; July 31, 2008 all amendments). The protocol of this study was first reviewed and approved by the Ethics Committee of Osaka City University Graduate School of Medicine, Osaka, Japan (No. 1227, 1297, 1385, and 1525), and by the Institutional Review Board/Ethics Committee at each study site. The study plan had been registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) before the first participant was enrolled (UMIN-CTR Identifier: UMIN000001194). All participants gave informed consent before enrollment.
Consent for publication
Availability of data and materials
No data is publicly available at present because data collection is still ongoing at the time of submission.
chronic kidney disease
chronic kidney disease-mineral bone disorder
full analysis set
fibroblast growth factor 23
- J-DAVID study:
Japan Dialysis Active vitamin D study
the Japanese Society for Dialysis Therapy
prospective randomized open-label blinded endpoint
randomized controlled trial
serious adverse events
source data verification
University Hospital Medical Information Network Clinical Trials Registry
vitamin D receptor activator
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The study design was presented as a poster (SA-PO2619) at the Kidney Week 2011 of the American Society of Nephrology (Philadelphia (PA)) and published as an abstract (J Am Soc Nephrol 22: 721A, 2011). The J-DAVID study was supported by many clinical research coordinators from the following site management organizations: Clinical Support Corporation (Tokyo), EP-Mint Co., Ltd. (Aichi), I’ROM Co., Ltd. (Tokyo), Medical Toyou Co., Ltd. (Kanagawa), Site Support Institute Co., Ltd. (Tokyo), Souken Co., Ltd. (Tokyo).
The J-DAVID study was funded by the grant from The Kidney Foundation, Japan.
T.S. received honorarium for lecturing and/or research grant from Asteras, Bayer, Boehringer Ingelheim, Chugai, Daiich Sankyo, Fuso, Kyowa Hakko Kirin (KHK), Mochida, MSD, Novo Nordisk, Pfizer, and Takeda Pharmaceutical. MI received research grant and/or honorarium for lecturing from Astellas, Bayer Yakuhin, Chugai, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, Mitsubishi Tanabe Pharma, MSD, Ono Pharmaceutical, Takeda Pharmaceutical, and Teijin Parma. Y.N. received honorarium for lecturing from Chugai, Kyowa Hakko Kirin, and Ono Pharmaceutical.
As the Steering Committee members, TS, MI, and YN contributed to the concept and design of the study, to organizing the study group, and to manuscript writing. All authors read and approved the final manuscript.
Study organization “J-DAVID Investigators”
The following list indicates the contributors’ names with institutions and prefectures in parenthesis:
Tetsuo Shoji* (Osaka City University, Osaka), Masaaki Inaba (Osaka City University, Osaka), and Yoshiki Nishizawa (Osaka City University, Osaka)
Tadao Akizawa (Showa University School of Medicine, Tokyo), Ryoichi Ando (Japanese Red Cross Musashino Hospital, Tokyo), Rieko Eriguchi (Fukuoka Renal Clinic, Fukuoka), Akira Fujimori (Konan Hospital, Hyogo), Masafumi Fukagawa (Tokai University, Kanagawa), Tetsuya Hashimoto (Tojinkai Hospital, Kyoto), Hideki Hirakata (Japanese Red Cross Fukuoka Hospital, Fukuoka), Hirokazu Honda (Showa University, Tokyo), Tatsuo Hosoya (Jikeikai University School of Medicine, Tokyo), Daijo Inaguma (Japanese Red Cross Nagoya Daini Hospital, Aichi), Toru Inoue (Higasikouri Hospital, Osaka), Yoshitaka Isaka (Osaka University Graduate School of Medicine, Osaka), Kunitoshi Iseki (University Hospital of the Ryukyus, Okinawa), Mari Ishida (Tokai University Hachioji Hospital, Tokyo), Eiji Ishimura (Osaka City University, Osaka), Noritomo Itami (Nikko Kinen Hospital, Hokkaido), Chiharu Ito (Haga Red Cross Hospital, Tochigi), Minoru Ito (Yabuki Clinic, Yamagata), Noriyuki Iwamoto (Tojinkai Hospital, Kyoto), Ryusuke Kakiya (Meijibashi Hospital, Osaka), Toshitaka Kakuta (Tokai University Hachioji Hospital, Tokyo), Toru Kawai (Chuou Naika Clinic, Hiroshima), Hideki Kawanishi (Tsuchiya General Hospital, Hiroshima), Shuzo Kobayashi (Shonan Kamakura General Hospital, Kanagawa), Kazutaka Kukita (Sapporo Hokuyu Hospital, Hokkaido), Junko Kumagai (Omachi Tsuchiya Clinic, Hiroshima), Eiji Kusano (JCHO Utsunomiya Hospital, Tochigi), Kiyoshi Maekawa (Fujiidera Shirasagi Clinic, Osaka), Ikuto Masakane (Yabuki Hospital, Yamagata), Hiroya Masaki (Kansai Medical University Hakii Hospital, Osaka), Mikio Okamura (Ohno Memorial Hospital, Osaka), Jun Minakuchi (Kawashima Hospital, Tokushima), Koji Mitsuiki (Japanese Red Cross Fukuoka Hospital, Fukuoka), Takashi Mizukuchi (Kochi Takasu Hospital, Kochi), Satoshi Morimoto (Tokyo Women’s Medical University, Tokyo), Yoshihiro Motomiya (Suiyukai Clinic, Nara), Takeshi Nakanishi (Hyogo College of Medicine, Hyogo), Tatsuya Nakatani (Osaka City University, Osaka), Tomohiko Naruse (Kasugai Municipal Hospital, Aichi), Shigeo Negi (Wakayama Medical University, Wakayama), Mitsushige Nishikawa (Kansai Medical University Internal Medicine II, Osaka), Kosaku Nitta (Tokyo Women’s Medical University, Tokyo), Tetsuya Ogawa (Tokyo Women’s Medical University Medical Center East, Tokyo), Seiji Ohira (Sapporo Kita Clinic, Hokkaido), Takayasu Ohtake (Shonan Kamakura General Hospital, Kanagawa), Senji Okuno (Shirasagi Hospital, Osaka), Toshihiko Ono (Tojinkai Hospital, Kyoto), Kazumichi Ota (Kochi Takasu Hospital, Kochi), Shigeru Otsubo (Sangenjaya Hospital, Tokyo), Toshinobu Sato (JCHO Sendai Hospital, Miyagi), Yuzuru Sato (Sato Junkankika Naika, Ehime), Takashi Shigematsu (Wakayama Medical University, Wakayama), Toshitsugu Sugimoto (Shimane University Faculty of Medicine, Shimane), Masashi Suzuki (Shinrakuen Hospital, Niigata), Tsutomu Tabata (Inoue Hospital, Osaka), Yoshio Taguma (JCHO Sendai Hospital, Miyagi), Hideki Tahara (Osaka City University, Osaka), Yoshiaki Takemoto (Osaka City University, Osaka), Kenji Tanaka (Suiyukai Clinic, Nara), Masaru Tanaka (Tanaka Kitanoda Hosipital, Osaka), Hideki Tanida (Yabuki Hospital, Yamagata), Masatomo Taniguchi (Kyushu University, Fukuoka), Yoshihiro Tominaga (Japanese Red Cross Nagoya Daini Hospital, Aichi), Yoshiharu Tsubakihara (Graduate School of Health Care Sciences, Jikei Insutitute, Osaka), Yoshihiro Tsujimoto (Inoue Hospital, Osaka), Kazuhiko Tsuruya (Graduate School of Medical Sciences, Kyushu University, Fukuoka), Yuzo Watanabe (Kasugai Municipal Hospital, Aichi), Kunihiro Yamagata (Faculty of Medicine, University of Tsukuba, Ibaraki), Tomoyuki Yamakawa (Shirasagi Hospital, Osaka), Shozo Yano (Shimane University, Shimane), Keigyou Yoh (University of Tsukuba, Ibaraki), Keitaro Yokoyama (Jikeikai University School of Medicine, Tokyo), Noriaki Yorioka (Hiroshima Kidney Organization, Hiroshima), Mitsuru Yoshimoto (Ohno Memorial Hospital, Osaka), Kenji Yuasa (Kochi Takasu Hospital, Kochi)
J-DAVID Research Group
The following list indicates J-DAVID study sites by prefecture from which one or more participants were enrolled, excluding the institutions of the Executive Committee members:
Aichi prefecture —Kazuhiro Fujisawa (Kasugai Central Clinic), Sumie Tawada (Kojukai Kasugai Hospital), Satoshi Yamaguchi (Seto Kyoritsu Clinic)
Chiba prefecture—Yasuho Kimura (Shin Kashiwa Clinic)
Fukushima prefecture —Hirofumi Nakano (Kashima Hospital)
Fukuoka prefecture —Itsuko Ishida (Harasanshin Hospital Gofukumachi Jin Clinic), Tetsuo Komota (Komota Clinic), Dai Matsuo (Hirao Clinic), Hiroaki Takamura (Hara Hospital)
Gunma prefecture —Kyoko Ito (Heisei Hidaka Clinic)
Hokkaid prefecture —Nobuo Hashimoto (H·N·Medic), Hironori Ishida (Kitasaito Hospital), Yoshitomo Itami (Higashi Muroran Satellite Clinic), Hirofumi Kon (KKR Sapporo Medical Center), Fumiaki Kumagai (Tomakomai Nissho Hospital)
Hyogo prefecture —Takuma Mabuchi (Tanaka Wadayama Clinic), Furuta Minoru (Aoi Hospital), Shiro Okajima (Tanaka Iin), Noriko Tanaka (Hojo Tanaka Hospital)
Ibaraki prefecture —Takashi Ishizu (Tsukuba Central Hospital), Takashi Ishizu (Central Jin Clinic Ryugasaki), Hiroshi Kikuchi (Kikuchi Medical Clinic), Masakazu Otsuka (Tokiwa Clinic), Atsushi Ueda (Namegata District General Hospital)
Kanagawa prefecture —Naoto Ishida (Seichi Clinic), Mikako Nagaoka (Honatsugi Medical Clinic), Ayaka Tanaka (Bousei Oone Clinic)
Kochi prefecture —Yasukazu Sen (Kochi Takasu Hospital Aki Clinic)
Kyoto prefecture —Naoto Adachi (Mabuchi Clinic), Masaki Koyama (Nishijin Hospital)
Miyagi prefecture —Kosei Kurosawa (Izumi Kurosawa Clinic), Akira Yuza (Dainohara Internal Medicine Clinic)
Oita prefecture —Kazuhiro Matsuyama (Matsuyama Iin Oita Nephrology Clinic), Makoto Matsuyama (Oita Nakamura Hospital)
Okayama prefecture —Masaki Fukushima (Shigei Medical Research Hospital)
Okinawa prefecture —Akira Higa (Shuri Jokamachi Clinic Daini), Kentaro Kohagura (University Hospital of the Ryukyus)
Osaka prefecture —Kaori Adachi (Kitatatsumi Shirasagi Clinic – Shirasagi Minami Clinic), Kiyoshi Goto (Ono Naika), Yuka Hosomi (Inoue Hospital), Noriko Kambara (Kanbara Hospital), Hironori Kawamura (Kawamura Clinic), Eiji Kimoto (Meijibashi Hospital), Satoshi Mikami (Higashikouri Hospital), Michiko Miura (Nagai Clinic), Harumi Nagayama (Nagayama Clinic), Koji Nakanishi (Nakanishi Clinic), Sei Nakatani (Ikuno Aiwa Hospital), Yasue Obi (Obi Clinic), Shigeki Okada (Okada Clinic), Mikio Okamura (Ohno Memorial Hospital), Nobuaki Okuda (Okuda Clinic), Senji Okuno (Shirasagi Clinic), Mayumi Sakurai (Jurakukai Clinic), Hidekazu Shimizu (Onoyama Clinic), Shigeichi Shoji (Shirasagi Hosipital), Kenzo Suzuki (Kadoma Clinic Aiwa Clinic), Akiko Tanaka (Tanaka Habikino Clinic), Keiko Tanaka (Kitahanada Clinic), Hitoshi Tanishita (Hanwa Memorial Hospital), Takeshi Wakikawa (Sakai Onshinkai Hospital), Ibuki Yajima (Ibuki Clinic), Yoshiaki Yamada (Arisawa General Hospital), Yasuo Yamakoshi (Ishikiriseiki Hospital), Shozo Yodoi (Yodoi Hospital)
Shimane prefecture—Yasutoshi Himeno (Himeno Clinic), Kazushi Shigeno (Ohda Himeno Clinic), Keiko Suzuki (Ohtsuka Clinic)
Tochigi prefecture —Ryuta Sato (Haga Red Cross Hospital)
Tokushima prefecture —Kazuhiko Kawahara (Kamojima Kawashima Hospital)
Tokyo prefecture —Hirokazu Honda (Ebara Clinic), Noritsugu Imamura (Minami-Tamachi Clinic), Naohiko Kato (Shinagawa Jin Clinic), Taku Morito (Towa Hospital), Seizo Murai (Iidabashi-Murai Iin), Shiori Osada (Tokyo Ayase Kidney Center), Jun Shiota (Kichijoji Asahi Hospital), Shinya Suganuma (Kidney Clinic Setagaya), Daijiro Uetake (Toyosu Kidney Dialysis Clinic), Ryo Yamamoto (Tateishi Jin Clinic)
Wakayama prefecture —Akio Kaketaka (Kihoku Clinic), Toshihiro Kodama (Kinokawa Clinic), Naoya Kodama (Kisen KD Clinic), Kunio Koshimura (Kumanoji Clinic), Akefumi Maeda (Kodama Hospital), Sadako Tamai (Taniguchi Hospital), Takuji Ujita (Ujita Circulation Disease Clinic)
Yamagata prefecture —Minoru Ito (Yabuki Hospital), Hideki Tanida (Tendo Onsen Yabuki Clinic)
Yoshinobu Hirayama1) (Osaka City University, Osaka), Taisuke Hojo2) (Osaka City University, Osaka), Toshiyoshi Tominaga3) (Osaka City University, Osaka), Yuichi Kato4) (Osaka City University, Osaka), Hisako Fujii5) (Osaka City University, Osaka)
1) 2008–2010, 2) 2010–2012, 3) 2012–2014, 4) 2014–2016, 5) 2008–2016
Mitsuru Fukui* (Osaka City University, Osaka)
Event Evaluation Committee
Hiroki Hase* (Toho University Ohashi Medical Center, Tokyo), Minoru Yoshiyama (Osaka City University, Osaka), Yuji Ikari (Tokai University School of Medicine, Kanagawa)
Independent Data Monitoring Committee
Shinichiro Ueda* (University of the Rryukus, Okinawa), Toyoaki Murohara (Nagoya University, Aichi), Shinichi Nishi (Kobe University, Hyogo)
Shinichiro Ueda* (University of the Rryukus, Okinawa), Toyoaki Murohara (Nagoya University, Aichi), Shinichi Nishi (Kobe University, Hyogo)
About this article
- Vitamin D
- Vitamin D receptor activator (VDRA)
- Cardiovascular disease
- Chronic kidney disease (CKD)
- Clinical trial