UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000030636
Receipt number R000034980
Scientific Title Vitamin D receptor activator versus intravenous calcimimetics in the treatment of renal patients with secondary hyperparathyroidism: a randomized clinical trial (VICTORY)
Date of disclosure of the study information 2018/01/01
Last modified on 2021/03/10 18:01:04

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Basic information

Public title

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

Acronym

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

Scientific Title

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

Scientific Title:Acronym

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

Region

Japan


Condition

Condition

Maintenance hemodialysis patients with secondary hyperparathyroidism

Classification by specialty

Endocrinology and Metabolism Nephrology Gastrointestinal surgery

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To compare the effects on serum calcification propensity (T50) between etercalcetide and vitamin D receptor activator (maxacalcitol) in the treatment of maintenance hemodialysis patients with secondary hyperparathyroidism

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV


Assessment

Primary outcomes

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

Key secondary 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 (all-cause death, hospitalization due to cardiovascular event, infection, and others)
9) Falls 12 months
10) Change in hand grip strength at 12 month from baseline
11) Changes in ability of daily living and cognitive function at 12 month from baseline


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

YES

Dynamic allocation

NO

Institution consideration


Blocking


Concealment

Central registration


Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Etelcalcetide (intravenous), thrice weekly, for 12 months.
Starting dose, 5 mg (thrice weekly). Dose adjustment according to the package insert.

Interventions/Control_2

Maxacalcitol (intravenous), thrice weekly, for 12 months.
Starting dose, 5 microg (thrice weekly) if intact PTH < 500 pg/mL; 10 microg (thrice weekly) if intact PTH >= 500 pg/mL. Dose adjustment according to the package insert.

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

80 years-old >

Gender

Male and Female

Key inclusion criteria

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, intravenous or oral vitamin D receptor activator in the preceding four weeks or longer

Key exclusion criteria

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

Target sample size

400


Research contact person

Name of lead principal investigator

1st name Tetsuo
Middle name
Last name Shoji

Organization

Osaka City University Graduate School of Medicine

Division name

Department of Vascular Medicine

Zip code

545-8585

Address

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

TEL

06-6645-3930

Email

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


Public contact

Name of contact person

1st name Shinya
Middle name
Last name Nakatani

Organization

Osaka City University Graduate School of Medicine

Division name

Department of Metabolism, Endocrinology and Molecular Medicine

Zip code

545-8585

Address

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

TEL

06-6645-3806

Homepage URL


Email

m2026719@med.osaka-cu.ac.jp


Sponsor or person

Institute

Osaka City University

Institute

Department

Personal name



Funding Source

Organization

ONO PHARMACEUTICAL CO., LTD.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Ethical Committee of Osaka City University Graduate School of Medicine

Address

1-5-7, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

Tel

06-6645-3456

Email

ethics@med.osaka-cu.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

大阪市立大学医学部附属病院(大阪府)、医療法人蒼龍会 井上病院(大阪府)、特定医療法人仁真会 白鷺病院(大阪府)、特定医療法人仁真会 白鷺診療所(大阪府)、特定医療法人仁真会 白鷺北巽クリニック(大阪府)、特定医療法人仁真会 白鷺南クリニック(大阪府)、特定医療法人仁真会 藤井寺白鷺クリニック(大阪府)、医療法人寿楽会 大野記念病院(大阪府)、医療法人寿楽会 寿楽会クリニック(大阪府)、医療法人藤井会 石切生喜病院(大阪府)、医療法人藤井会 住道クリニック(大阪府)、社会医療法人景岳会 南大阪クリニック(大阪府)、医療法人垣谷会 明治橋病院(大阪府)、医療法人 淀井病院(大阪府)、 医療法人宝持会 池田病院(大阪府)、医療法人宝持会 いけだクリニック(大阪府)、医療法人岡田会 岡田クリニック(大阪府)、医療法人徳靖会 小尾クリニック(大阪府)、医療法人恵仁会 小野内科医院(大阪府)、特定医療法人三和会 永山クリニック(大阪府)、医療法人 佐々木内科クリニック(大阪府)、野崎クリニック(大阪府)、医療法人 河村クリニック(大阪府)、マリエ医院(大阪府)


Other administrative information

Date of disclosure of the study information

2018 Year 01 Month 01 Day


Related information

URL releasing protocol

https://jrct.niph.go.jp/re/reports/detail/9902

Publication of results

Published


Result

URL related to results and publications

https://jrct.niph.go.jp/re/reports/detail/9902

Number of participants that the trial has enrolled

326

Results

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.

Results date posted

2021 Year 02 Month 28 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2021 Year 03 Month 08 Day

Baseline Characteristics

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.

Participant flow

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.

Adverse events

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.

Outcome measures

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.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2017 Year 09 Month 29 Day

Date of IRB

2017 Year 11 Month 27 Day

Anticipated trial start date

2018 Year 02 Month 01 Day

Last follow-up date

2020 Year 01 Month 09 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information

The results of this trial have been published online on March 8, 2021: https://cjasn.asnjournals.org/content/early/2021/03/05/CJN.16601020


Management information

Registered date

2017 Year 12 Month 29 Day

Last modified on

2021 Year 03 Month 10 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034980


Research Plan
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Research case data specifications
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Research case data
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