UMIN-CTR Clinical Trial

Public title

Effects of Rivaroxaban on Renal Function in Non-valvular atrial Fibrillation Patients with Chronic Kidney Diseases

Acronym

X-NOAC Study

Scientific Title

Effects of Rivaroxaban on Renal Function in Non-valvular atrial Fibrillation Patients with Chronic Kidney Diseases

Scientific Title:Acronym

X-NOAC Study

Region

Japan

Condition

Non-valvular atrial Fibrillation Patients with Chronic Kidney Diseases

Classification by specialty

Medicine in general	Cardiology	Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To determine whether rivaroxaban would have an impact on the renal function in patients with non-valvular atrial fibrillation compared to warfarin.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The primary endpoint was the change amount in urinary albumin 3 months after registration.

Key secondary outcomes

The secondary endpoints were changes amount in endothelial functions, inflammatory markers, renal function markers, osteocalcin markers.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

rivaroxaban group

Interventions/Control_2

warfarin group

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

30

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Inclusion criteria
(1)Age>- 30 years old.
(2)Patients who had initiated anticoagulation therapy or patients who had already received warfarin therapy.
(3)estimated glomerular filtration rate > 30 and < 60 mL/min/1.73 m2: CKD grade G2 to G3b.

Key exclusion criteria

Patients meeting any of the following criteria were not eligible for inclusion in this study.
(1)Patients with onset of acute coronary syndrome or stroke within 6 months.
(2)Patients scheduled to undergo percutaneous coronary intervention (PCI) or catheter ablation.
(3)Patients receiving dual ntiplatelet therapy (DAPT).
(4)Patients with a history of hypersensitivity to the components of warfarin or rivaroxaban.
(5)Patients with active bleeding (non-major clinically relevant bleeding events, such as intracranial hemorrhage, gastrointestinal hemorrhage).
(6)Patients with hepatic disorders associated with coagulation abnormalities.
(7)Patients with moderate or severe hepatic disorder (equivalent to Child-Pugh classification B or C).
(8)Patients with renal failure (creatinine clearance < 30 mL/min).
(9)Pregnant women or women with pregnancy potential.
(10)Patients receiving HIV protease inhibitors (ritonavir, atazanavir, indinavir, etc.).
(11)Patients receiving oral or intravenous administration of azole antifungal drugs (itraconazole, voriconazole, or ketoconazole).
(12)Patients receiving vitamin K agents for osteoporosis.
(13)Patients receiving iguratimod.
(14)Patients with acute bacterial endocarditis.
(15)Patients who did not give informed consent.
(16)Other patients considered by the investigator to be unsuitable for participation in the study.

Target sample size

160

Name of lead principal investigator

1st name	Koichi
Middle name
Last name	Node

Organization

Saga University Faculty of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

8498501

Address

5-1-1 Nabeshima, Saga-shi, Saga

TEL

0952-34-2364

Email

node@cc.saga-u.ac.jp

Name of contact person

1st name	Koichi
Middle name
Last name	Node

Organization

Saga University Faculty of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

8498501

Address

5-1-1 Nabeshima, Saga-shi, Saga

TEL

0952-34-2364

Homepage URL

Email

node@cc.saga-u.ac.jp

Institute

Saga University Faculty of Medicine, Department of Cardiovascular Medicine

Institute

Department

Personal name

Organization

Bayer Yakuhin, Ltd

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Kameda Medical Center
Tokyo Metropolitan Hiroo Hospital
Dokkyo Medical University Saitama Medical Center
Yokohama Minami Kyousai Hospital
Imari Arita Kyoritsu Hospital

Name of secondary funder(s)

Organization

Clinical Research Center,Saga University Hospital

Address

5-1-1 Nabeshima,Saga

Tel

0952343357

Email

kenkyu-shinsei@ml.cc.saga-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

佐賀大学医学部附属病院（佐賀県）、亀田総合病院（千葉）、都立広尾病院（東京）、獨協医科大学埼玉医療センター（埼玉）、横浜南共済病院(神奈川)、伊万里有田共立病院(佐賀）

Date of disclosure of the study information

2015

Year

01

Month

21

Day

URL releasing protocol

https://www.sciencedirect.com/science/article/pii/S0167527315007561?via%3Dihub

Publication of results

Published

URL related to results and publications

https://www.nature.com/articles/s41440-019-0384-6

Number of participants that the trial has enrolled

58

Results

There was no significant intergroup difference in the magnitude of changes in UACR (p=0.52).

Results date posted

2020

Year

07

Month

29

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The mean age was 72.3+-7.6 years old in the rivaroxaban group (female n=2[8.0%]), and the mean age was 70.7+-9.0 years old in the warfarin group(female n=2[7.7%]).

Participant flow

A total of 58 patients were enrolled in the study (30 in the rivaroxaban group and 28 in the warfarin group). Among them, 26 cases (rivaroxaban group) and 26 cases (warfarin group) were included in the safety analysis set, and 25 cases (rivaroxaban group) and 26 cases (warfarin group) were included in the full analysis set.

Adverse events

No adverse events were observed.

Outcome measures

The change amount in urinary albumin 3 months after registration: -1.4 [23.5, 0.9] (rivaroxaban group) vs. -0.4 [12.2, 4.6] (warfarin group), p=0.52.

The changes amount in renal markers (eGFR, Cistatin C, L-FABP): -0.5 [-6.2, 2.8] (rivaroxaban group) vs. -0.6 [-4.4, 5.0] (warfarin group), p=0.50 (eGFR); 0.0 [-0.1, 0.1] (rivaroxaban group) vs. 0.0 [-0.1, 0.1] (warfarin group), p=0.58 (Cistatin C); -0.1 [-0.8, 0.7] (rivaroxaban group) vs. 0.4 [-0.4, 1.7] (warfarin group), p=0.31 (L-FABP).

The changes amount in endothelial function (RHI): 0.1 [-0.1, 0.5] (rivaroxaban group) vs. 0.2 [-0.2, 0.5] (warfarin group), p=0.65.

The changes amount in inflammatory marker (PTX3): 0.0 [-0.2, 0.3] (rivaroxaban group) vs. 0.0 [-0.4, 0.5] (warfarin group), p=1.00.

The changes amount in osteocalcin: 0.7 [-0.9, 2.5] (rivaroxaban group) vs. 0.2 [-0.9, 1.8] (warfarin group), p=0.52.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

10

Month

08

Day

Date of IRB

2014

Year

11

Month

10

Day

Anticipated trial start date

2015

Year

03

Month

01

Day

Last follow-up date

2018

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2015

Year

01

Month

21

Day

Last modified on

2022

Year

08

Month

25

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018907