Japanease

Mar. 25, 2019

Jan. 27, 2021

jRCTs051180156

Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)

Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)

Dec. 27, 2019

326

The number of participants, sex, diabetic nephropathy, age, duration of hemodialysis, serum intact PTH, corrected calcium, and phosphate levels of the two groups in the full analysis set were as follows [percentage for categorical variables, median (interquartile range) for continuous variables]: < Etelcalcetide group > Total N 165, Men 110 (66.7%), Diabetic nephropathy 69 (41.8%), Age 66 (55-71) years, Duration of hemodialysis 6.2 (3.1-14.8) years, serum intact PTH 418 (313-563) pg/mL, corrected calcium 9.20 (8.80-9.60) mg/dL, phosphate 5.50 (4.60-6.20) mg/dL. < VDRA group > Total N 156, Men 98 (62.8%), Diabetic nephropathy 56 (35.9%), Age 66 (57-71) years, Duration of hemodialysis 7.1 (3.7-14.3) years, serum intact PTH 436 (338-600) pg/mL, corrected calcium 9.20 (8.88-9.50) mg/dL, phosphate 5.60 (4.88-6.62) mg/dL.

Enrollment was done at an expected pace. The target number of participants was 400, and 425 patients were provisionally enrolled. After washout of medication following provisional enrollment, 99 patients did not meet the eligibility criteria and excluded. The final number of enrolled patients was 326 (167 in the etelcalcetide group and 159 in the VDRA group). In the etelcalcetide group, 1 was excluded because of eligibility, and 1 was excluded because the patient declined to receive. The assigned treatments were received in 165 patients in the etelcalcetide group and in 159 patients in the VDRA group. Safety analysis set included 165 patients in the etelcalcetide group and 159 patients in the VDRA group. Full analysis set included 165 patients in the etelcalcetide group and 156 patients in the VDRA group. Per-protocol set included 164 patients in the etelcalcetide group and 155 patients in the VDRA group.

Safety evaluation was done in the safety analysis set (Etelcalcetide group N = 165, VDRA group N = 159). This study examined SAEs, symptoms (nausea, vomiting, dysgeusia, diarrhea, itching, irritability), falls, hypercalcemia requiring temporal cessation of study drug, and hypocalcemia requiring temporal cessation of study drug. The safety results were as indicated below: (1) SAEs: Etelcalcetide group 41 events (32 cases, 19.4%) VDRA group 70 events (44 cases, 27.7%) (2) Symptoms Nausea: Etelcalcetide group 11 events (9 cases, 5.5%) VDRA group 24 events (17 cases, 10.7%) Vomiting: Etelcalcetide group 10 events (8 cases, 4.8%) VDRA group 16 events (12 cases, 7.5%) Dysgeusia: Etelcalcetide group 7 events (4 cases, 2.4%) VDRA group 5 events (3 cases, 1.9%) Diarrhea: Etelcalcetide group 22 events (16 cases, 9.7%) VDRA group 10 events (7 cases, 4.4%) Itching: Etelcalcetide group 58 events (30 cases, 18.2%) VDRA group 72 events (38 cases, 23.9%) Irritability: Etelcalcetide group 20 events (15 cases, 9.1%) VDRA group 24 events (16 cases, 10.1%) (3) Falls: Etelcalcetide group 47 events (28 cases, 17.0%) VDRA group 38 events (27 cases, 17.0%) (4) Hypercalcemia-hypocalcemia requiring temporal cessation of study drug Hypercalcemia requiring temporal cessation of study drug Etelcalcetide group 0 events (0 cases, 0%) VDRA group 10 events (10 cases, 6.3%) Hypocalcemia requiring temporal cessation of study drug Etelcalcetide group 33 events (30 cases, 18.2%) VDRA group 0 events (0 cases, 0%) Among the above (1) through (4), hypercalcemia-hypocalcemia requiring cessation of study drug was adjudicated to be related to study drugs, whereas the SAEs, symptoms, or falls were not considered to be related to study drugs.

The primary, secondary and tertiary outcomes were the change in T50 (deltaT50), the changes in hand grip strength, and the change in cognition-ADL assessed by DASC-21 in 12 months of treatment, and these outcomes were compared between the etelcalcetide group (Intervention group) and the intravenous VDRA (maxacalcitol, Control group). deltaT50 was significantly greater in the etelcalcetide group, with the difference of 20 (7 to 34) minutes [difference (95% confidence interval), P = 0.004]. No significant difference was found in the change in hand grip strength [0.16 (-0.87 to 1.10) kg, P = 0.756] or in the DASC-21 score [-0.55 (-1.58 to 0.47) points, P = 0.291] between the two groups.

Etelcalcetide was more effective in increasing T50 than maxacalcitol in hemodialysis patients with secondary hyperparathyroidism. There was no difference in the effects on hand grip strength or cognition between of the two drugs.

Dec. 26, 2020

Yes

Individual participant data that underline the results reported in this article (text, tables, figures and appendices), after deidentification, study protocol and statistical analysis plan will be shared with researchers who provide a methodologically sound proposal to achieve aims in the approved proposal. Data sharing will be available in a period beginning three months and ending 5 years following article publication. Proposal should be directed to t-shoji@med.osaka-cu.ac.jp.

https://jrct.niph.go.jp/latest-detail/jRCTs051180156

Shoji Tetsuo

Osaka City University Hospital

1-5-7, Asahi-machi, Abeno-ku, Osaka 545-8586

+81-6-6645-3930

t-shoji@med.osaka-cu.ac.jp

Nakatani Shinya

Osaka City University Graduate School of Medicine

1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585

+81-6-6645-3806

m2026719@med.osaka-cu.ac.jp

Feb. 28, 2018

400

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

none

1) Men and women, age >= 20 and < 80 years
2) Duration of dialysis >= 90 days
3) Serum intact PTH >= 241 pg/mL and corrected Ca >= 8.4 mg/dL
4) Treated 3 times a week of hemodialysis
5) No treatment with etelcalcetide, cinacalcet, evocalcet, intravenous or oral vitamin D receptor activator in the preceding four weeks or longer

1) History of parathyroid intervention or fracture in the preceding 12 weeks
2) History of myocardial infarction, stroke, lower limb amputation, or revascularization for coronary artery or lower extremity in the preceding 12 weeks
3) Presence of heart failure of NYHA class III or IV
4) Presence of respiratory failure of SpO2 <90%
5) Patients with severe illness with life expectancy of less than 1 year
6) Liver dysfunction with elevated AST or ALT exceeding 3 x upper limit of normal
7) Pregnant, lactating women or women who plan to be pregnant
8) History of allergy to etercalcetide and/or maxacalcitol
9) Patients treated with bisphosphonate and/or denosumab

20age old over
80age old not

Both

Maintenance hemodialysis patients with secondary hyperparathyroidism

Vitamin D receptor activator, calcimimetics

Medicine

End-stage kidney failure, hemodialysis, secondary hyperparathyroidism

Change in T50 (delta T50) at 12 month from baseline

< Secondary outcome >
Change in hand grip strength at 12 month from baseline
< Tertiary outcome >
Changes in ability of daily living and cognitive function at 12 month from baseline
< Other subsidiary outcomes >
1) Changes in T50 (delta T50) at 3 and 6 month from baseline
2) Proportions of participants who achieve the target ranges of serum Ca, P and intact PTH, respectively, by the JSDT CKD-MBD guideline (2012) at 3, 6 and 12 month
3) Proportions of participants who have the reduction of intact PTH level by 30% or greater at 3, 6 and 12 month
4) Ca-P product at 3, 6 and 12 month
5) Serum Fetuin A and FGF23 levels at 3, 6 and 12 month
6) Subjective symptoms (nausea, vomiting, cacogeusia, diarrhea, and jitteriness)
7) Hypocalcemia and hypercalcemia requiring cessation of the study drug
8) Severe adverse events in 12 months (allcause death, hospitalization due to cardiovascular event, infection, and others)
9) Falls in 12 months

Complete

ONO PHARMACEUTICAL CO., LTD.
Not applicable
Osaka City University Hospital Certified Review Board
Abeno Medix 6th floor, 1-2-7 Asahi-machi, Abeno-Ku, Osaka, Osaka

+81-6-6645-3456

irb@med.osaka-cu.ac.jp
Approval

Feb. 21, 2019

UMIN000030636
UMIN Clinical Trials Registry (UMIN-CTR)