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Development of treatment strategy for CKD-MBD by multilateral mechanism of etelcalcetide hydrochloride (The DUET study)

Development of treatment strategy for CKD-MBD by multilateral mechanism of etelcalcetide hydrochloride (the DUET study)

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The median age was 69 years (34-94). 84 males and 40 females. The median dialysis vintage was 6.19 years (1-44). A median iPTH was 271 pg / dL (96-717) at baseline.

Registration proceeded as planned without delay. Forty-one patients were assigned to the etelcalcetide + vitamin D group (E + D), 41 to the etelcalcetide + oral calcium group (E + Ca), and 42 to the control group (Control). Forty in Group E + D, 37 in Group E + Ca, and 41 in control completed this trial.

One death. 9 hospitalization (including extension of scheduled hospitalization) The causal relationship between these events and this study drug has been denied. There were 18 other adverse events.

The patients reaching the primary endpoint (95 % confidential interval: CI) were 90.0 % (76.3-97.2) in Group E+D, 56.8 % (39.5-72.9) in Group E+Ca, and 19.5 % (8.8-34.9) in Group C. The treatment of etelcalcetide demonstrated a significant increase in the number of patients achieving the endpoint (odds ratio 13.4; CI 5.10-35.3) in logistic regression analysis with iPTH, corrected serum calcium, and phosphate at baseline as covariates. Significantly more patients achieved the endpoint in Group E+D as compared to those in Group E+Ca (odds ratio 6.35; CI 1.79-22.48). In the linear mixed model, serum levels of FGF23 in etelcalcetide users were significantly lower than those in non-users at week 6 (p < 0.001) and week 12 (p < 0.001). When compared the difference between the E+Ca group and the E+D group, serum levels of FGF23 in the E+Ca group were significantly lower than those in the E+D group at week 12 (p = 0.017). There were no significant differences in the serum levels of CPPs between etelcalcetide users and non-users at week 6 (p = 0.10) and week 12 (p = 0.18), while CPPs in the E+Ca group were significantly lower than those in the E+D group (p < 0.001) at week 12.

Among MHD with SHPT, the use of etelcalcetide showed good control of iPTH. Active active vitamin D was useful in correcting hypocalcemia while oral calcium preparation was superior in suppressing hyperphosphatemia. To reduce cardiovascular disease risks, etelcalcetide may be useful through suppression of FGF23 levels. When correcting hypocalcemia, loading oral calcium preparations could be recommended for the suppression of both FGF23 and CPPs.

Sept. 08, 2022

Sept. 18, 2020

https://www.sciencedirect.com/science/article/pii/S2468024920315254?via%3Dihub

No

No

https://jrct.niph.go.jp/latest-detail/jRCTs041180108

Maruyama Shoichi

Nagoya University Graduate School of Medicine

65 Tsurumai-cho, Showa-ku, Nagoya

marus@med.nagoya-u.ac.jp

Kato Sawako

Nagoya University Graduate School of Medicine

65 Tsurumai-cho, Showa-ku, Nagoya

+81-52-744-2192

kato07@med.nagoya-u.ac.jp

Complete

Feb. 22, 2018

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1.patients on maintenance hemodialysis 3 times a week
2.patients with more than one-year hemodialysis vintage
3.patients who are judged stable
4.older than 20 years and younger than 100 years
5.iPTH >=240 pg/ml within 4 months
6.corrected Ca >=8.4mg/dl at enrollment
7.patients who are able to write informed consent

1.patients who have been prescribed etelcalcetide before
2.bisphosphonate users within 24 weeks
3.primary hyperparathyroidism
4.undergoing parathyroidectomy or intervention therapy to parathyroid within 90 days before enrollment
5.scheduled parathyroidectomy, intervention therapy to parathyroid or kidney plantation
6. pregnant or breast feeding
7. patients who are deemed unsuitable by a physician, for instance cancer, severe infection and severe complication
8. patients who are prescribed Maxacalcitol, over 10[micro]gx3/week at obtainment of IC
9. patients who are prescribed Calcitriol, over 0.75[micro]gx3/week at obtainment of IC
10. patients who are prescribed other active VitD, over half of maximum dose at obtainment of IC
11. patients who are prescribed precipitated calcium carbonate, over 3g/day at obtainment of IC

Both

Secondary hyperparathyroidism

am A: Etelcalcetide+active Vitamin D
am B: Etelcalcetide+oral calcium (calcium carbonate)
am C: Control [active Vitamin D + oral calcium (calcium carbonate)]

Ratio of achievement of more than 50% reduction and under 240pg/dl in intact parathyroid hormone (iPTH) after 12 weeks of treatment

-Ratio of achievement of 60<=iPTH<=240 after 12 weeks of treatment
-Ratio of achievement of more than 30% reduction in iPTH after 12 weeks of treatment
-Ratio of achievement of more than 30% reduction and 60<=iPTH<=240 after 12 weeks of treatment
-Ratio of achievement of more than 50% reduction in iPTH after 12 weeks of treatment
-Change in iPTH after 2, 4, 6, 8, 10 and 12 weeks of treatment relative to the baseline
-Change in CalciProtein Particle (CPP) and Fibroblast Growth Factor 23 (FGF23) after 6 and 12 weeks of treatment relative to the baseline among treatment groups
-Change in Ca, P, CaXP and Mg after2, 4, 6, 8, 10 and 12 weeks relative to the baseline among treatment groups
-Change in Bone Specific Alkaline Phosphatase (BAP) and Tartrate-resistant Acid Phosphatase 5b (TRACP5b) after one year of treatment relative to the baseline among treatment groups
-Comparison of aortic calcification before and after observation
-Ca, P and iPTH levels after one year of treatment
-Comparison of normalized ratio of hypocalcemia between VitD and calcium preparations
-Adverse events

+81-52-744-2479

Feb. 04, 2019

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