UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000014222
Receipt number R000016553
Scientific Title Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis; a multicentre, open label, randomised control trial
Date of disclosure of the study information 2014/08/01
Last modified on 2022/12/15 11:42:41

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Basic information

Public title

Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis; a multicentre, open label, randomised control trial

Acronym

LoVAS

Scientific Title

Low-dose glucocorticoids plus rituximab versus high-dose glucocorticoids plus rituximab for remission induction in ANCA-associated vasculitis; a multicentre, open label, randomised control trial

Scientific Title:Acronym

LoVAS

Region

Japan


Condition

Condition

ANCA-associated vasculitis

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To demonstrate non-inferiority of efficacy of low-dose glucocorticoids plus rituximab against high-dose glucocorticoids plus rituximab in remission induction in ANCA-associated vasculitis

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2


Developmental phase

Phase IV


Assessment

Primary outcomes

Proportion of the patients achieving remission within 6 months

Key secondary outcomes

<Efficacy>
(1) Time to remission
(2) Overall survival, disease free survival, time to end-stage renal disease, time to the first serious adverse event
(3) Proportions of death, relapse, end-stage renal disease and the composite of these (6 months and 24 months)
(4) Proportions of severe relapse
(5)Proportions of the patients achieving remission and stopping glucocorticoids
(6) BVAS ver3
(7) VDI
(8) SF-36
(9) Patient global assessment (visualised analogue scale)
(10) accumulative dose of glucocorticoids
<safety>
(1) Numbers of events of adverse events/serious adverse events, proportions of the patients with adverse events/serious adverse events
(2) Proportions of the patients with new onset diabetes mellitus, hypertension and hyperlipidemia
(3) Proportion of the patients with new onset insomnia
(4) Proportion of the patients with new onset bone fracture, bone density
(5) Number of infections, proportions of the patients with infection
<Exploratory>
(1) Serum immunoglobulin levels
(2) Peripheral blood B cell counts
(3) MPO-/PR3-ANCA levels


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking


Concealment



Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

low-dose glucocorticoids plus rituximab
(prednisolone0.5mg/kg/day+rituximab375mg/m2/wx4)

Interventions/Control_2

high-dose glucocorticoids plus rituximab
(prednisolone1.0mg/kg/day+rituximab375mg/m2/wx4)

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


Not applicable

Gender

Male and Female

Key inclusion criteria

To be included in the trial patients must must have:
(1) Provision of written informed consent by a patient or a surrogate decision maker
(2) Age=>20 years
(3) New clinical diagnosis of ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis or renal limited vasculitis) consistent with the 2012 Chapel Hill consensus definitions
(4) Positive test by ELISA for proteinase 3-ANCA or myeloperoxidase-ANCA

Key exclusion criteria

The presence of any of the following will preclude patient inclusion:
(1) Prior treatment for ANCA-associated vasculitis before trial entry
(2) ANCA-associated vasculitis related glomerulonephritis (eGFR<15ml/min) or alveolar hemorrhage (oxygen inhalation >2L/min)
(3) Presence of another multisystem autoimmune disease
(4) Known infection with HIV; a past or current history of hepatitis B virus or hepatitis C virus infection
(5) Desire to bear children, pregnancy or lactating
(6) History of malignancy within the past 5 years or any evidence of persistent malignancy
(7) Ongoing or recent (last 1 year) evidence of active tuberculosis
(8) Severe allergy or anaphylaxis to monoclonal antibody therapy
(9) Any concomitant condition anticipated to likely require oral systemic glucocorticoids, immunosuppressants, biologics, plasma exchange or IVIg
(10) Any biological B cell depleting agent (such as rituximab or belimumab) within the past 6 months
(11) Other conditions, in the investigator's opinion, inappropriate for the trial entry

Target sample size

140


Research contact person

Name of lead principal investigator

1st name Hiroshi
Middle name
Last name Nakajima

Organization

Chiba University Hospital

Division name

Allergy and Clinical Immunology

Zip code

2608670

Address

1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

TEL

043-222-7171

Email

nakajimh@faculty.chiba-u.jp


Public contact

Name of contact person

1st name Shunsuke
Middle name
Last name Furuta

Organization

Chiba University Hospital

Division name

Clinical Research Center

Zip code

2608670

Address

1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

TEL

043-222-7171

Homepage URL


Email

shfuruta@chiba-u.jp


Sponsor or person

Institute

Chiba University Hospital

Institute

Department

Personal name



Funding Source

Organization

Chiba University Hospital

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Chiba University Hospital

Address

1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

Tel

043-222-7171

Email

shiken@office.chiba-u.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



Other administrative information

Date of disclosure of the study information

2014 Year 08 Month 01 Day


Related information

URL releasing protocol

https://www.m.chiba-u.jp/dept/allergy-clin-immunol/files/3315/9893/5994/protocol_2.5.pdf

Publication of results

Published


Result

URL related to results and publications

https://clinicaltrials.gov/ct2/show/NCT02198248

Number of participants that the trial has enrolled

140

Results

Remission rates: Low-dose group 71% vs High-dose group 69%

Results date posted

2022 Year 12 Month 15 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

Reduced-dose (n = 69) vs High-dose (n = 65)
Age, median, y 73 vs 74
Female 43 vs 37
Male 26 vs 28
Microscopic polyangiitis 53 vs 51
Granulomatosis with polyangiitis 16 vs 13
Renal-limited vasculitis 0 vs 1

Participant flow

Between November 2014 and June 2019, a total of 140 patients with ANCA-associated vasculitis were enrolled in this study. Of these patients, 70 were randomly assigned to receive the reduced-dose regimen and 70 to receive the high-dose regimen. Five in the high-dose group and 1 in the reduced-dose group were excluded from analysis. There was 1 dropout in each treatment group.

Adverse events

Twenty-one serious adverse events occurred in 13 patients in the reduced-dose group (18.8%), while 41 occurred in 24 patients in the high-dose group (36.9%). Seven serious infections occurred in 5 patients in the reduced-dose group (7.2%), while 20 occurred in 13 patients in the high-dose group (20.0%).

Outcome measures

Reduced-dose (n = 69) vs High-dose (n = 65)
Relapse 9 vs 5
Deaths 2 vs 5
End-stage kidney disease 0 vs 1

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2014 Year 06 Month 18 Day

Date of IRB

2014 Year 06 Month 18 Day

Anticipated trial start date

2014 Year 09 Month 30 Day

Last follow-up date

2021 Year 09 Month 30 Day

Date of closure to data entry

2021 Year 12 Month 30 Day

Date trial data considered complete

2022 Year 03 Month 30 Day

Date analysis concluded

2022 Year 03 Month 30 Day


Other

Other related information



Management information

Registered date

2014 Year 06 Month 10 Day

Last modified on

2022 Year 12 Month 15 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016553


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name