UMIN-CTR Clinical Trial

Public title

Effect of SGLT2 inhibitor (Lusefi) on diabetic nephropathy
Stratified analysis based on different original renal function category

Acronym

CHAT-Lu

Scientific Title

Effect of SGLT2 inhibitor (Lusefi) on diabetic nephropathy
Stratified analysis based on different original renal function category

Scientific Title:Acronym

CHAT-Lu

Region

Japan

Condition

Type 2 diabetes mellitus

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Long term time course effect of SGLT2 inhibitor (Lusefi) on renal function (eGFR)

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Renal function at 104th week post SGLT2 inhibitor treatment
Stratified analysis based on different original renal function category

Key secondary outcomes

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Oral treatment of SGLT2 inhibitor(Lusefi)2.5mg once a day for 104 weeks

Interventions/Control_2

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

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Type 2 diabetes mellitus(HbA1c 6.5%<=)
pre eGFR(30-90ml/min/1.73m2)
age 20 years old <=

Key exclusion criteria

past use of SGLT2 inhibitor
severe ketoacidosis,diabetes coma,type1diabetes
severe infection,pre and post operation,severe in injury
pregnancy,lactation,potential pregnancy

Target sample size

100

Name of lead principal investigator

1st name	Hidenori
Middle name
Last name	Urata

Organization

Fukuoka University Chikushi Hospital

Division name

Cardiovascular internal medicine

Zip code

8188502

Address

1-1-1,Zokumyoin,Chikushino Fukuoka

TEL

092-921-1011

Email

uratah@fukuoka-u.ac.jp

Name of contact person

1st name	Hidenori
Middle name
Last name	Urata

Organization

Fukuoka University Chikushi Hospital

Division name

Cardiovascular internal medicine

Zip code

8188502

Address

1-1-1,Zokumyoin,Chikushino Fukuoka

TEL

092-921-1011

Homepage URL

Email

uratah@fukuoka-u.ac.jp

Institute

Fukuoka University Chikushi Hospital

Institute

Department

Personal name

Organization

Tisho Toyama Pharmaceutical co,Ltd

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kyoto Prefectural University of Medicine, Clinical Research Review Board

Address

465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto

Tel

0752515337

Email

rinri@koto.kpu-m.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

Date of disclosure of the study information

2018

Year

01

Month

04

Day

URL releasing protocol

https://jrct.niph.go.jp

Publication of results

Published

URL related to results and publications

https://jrct.niph.go.jp

Number of participants that the trial has enrolled

53

Results

There was no significant decrease in eGFR over 2 years, demonstrating renoprotective effects of luseogliflozin in patients with type 2 diabetes. Changes in eGFR were not correlated with changes in HbA1c. On the other hand, luseogliflozin had lesser renal protective effect in patients with overt proteinuria. In this study, blood sugar lowering effect, blood pressure lowering effect, liver function improving effect, and weight loss effect were also observed.

Results date posted

2023

Year

04

Month

07

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Luseogliflozin was administered to type 2diabetes mellitus patients who received written consent from the patient during outpatient visits to Fukuoka University Chikushi Hospital or to
the registered practitioners with the Chikushi Cardiovascular Clinical Research Network (Chikushi-JRN). From 3 April 2018 to 23 December 2019, 53 patients were enrolled at 5 sites and 46 patients who were able to continue Luseogliflozin up to 104 weeks were analyzed. The mean age was 66.2 years, 56.6% of men, and the mean duration of diabetes was 8.1 years. Averaged
BMI was 27, so that rather obesity patients were entered. As for complicated diseases, hypertension and dyslipidemia were found in about 60% of cases. DPP-4 inhibitors were the most common hypoglycemic drugs used at the start at 41.5%, followed by biguanides at 22.6%.

Participant flow

Due to the fact that it was a fairly late start of sales as an SGLT2 inhibitor and the delay in the start of case enrollment due to the overlap of this study at a time when it had to be performed as Specified Clinical Research, the case registration was sluggish and the target number of cases of 100 cases could not be reached, resulting in 53 cases being registered. Since this is a prospective clinical single-arm study without a control group, it proves the hypothesis that renal function does not decrease significantly after initiation of SGLT2 inhibitors.
Although the number of registered cases was about half, stratified analysis by renal function at the start of the study determined that it was possible to conclude and judge whether this
drug could be used for the purpose of maintaining renal function for at least 2 years even in the group with relatively low renal function. The recruitment ended during the scheduled recruitment period and was observed for 2 years. During that period, as shown in 9, a total of seven patients were canceled, including 3 cases of discontinuation due to disease outbreaks, 1 case of protocol dropout, 1 case of discontinuation due to transfer, and 2 cases of discontinuation due to no visit.

Adverse events

There were three cases of illness in total. There was one death, one worsening of HbA1c, and one stroke. There were no mild or serious adverse events attributable to the drug. The details are as follows.

Case 1: Death Death from malignant lymphoma not related to medication of the study.

Case 2: Worsening of HbA1c After receiving Luseoglifrogin, it was discontinued due to continued increase in Hba1c levels, despite good improvement in factors other than HbA1c. The cause is
unknown, and the causal relationship with the administered drug is not clear.

Case 3: Cerebral infarction There is no clinical report that the appearance of stroke in cases using SGLT-2 inhibitors decreases compared to the placebo group, and the cerebral infarction in this case is considered to be a spontaneous onset with a consistent course of occurrence. This case has a history of diabetes, dyslipidemia, and administration of
Luseoglifrogin has been started since April 5, 2019. At the start of treatment, HbA1 was 6.8%, blood pressure was normal, and other laboratory tests showed no renal dysfunction or dehydration except for a high triglyceride level of 252 mg/dL. The onset of cerebral infarction occurred on December 12, 2019, eight months after the start of Luseoglifrogin administration.
According to a report from a practicing physician, this case had a speech disorder and paralysis of the right lower limb when he woke up, so he was examined by a nearby brain surgeon and was transferred to a local core hospital with a diagnosis of cerebral infarction with JCS 1st degree. He showed hemiplegia including the right face and cerebral infarction in the left radiating crown at MRI. After that, the clinical findings improved and he was discharged, and after home treatment, he went to a nearby doctor who was a field doctor and is currently doing well. There are no data on the onset of cerebral infarction, and it is not clear whether dehydration occurred.

Outcome measures

There was no significant reduction in eGFR74.6ml/min/1.73m2 at the start, 74.4 plus orminus 21.5 ml/min/l. 73 m2 after 52 weeks, and75.8 plus or minus 20.8 ml/min/l. 73 m2 after 104 weeks　compared to that at the start of treatment (n.s.). eGFR at start less than 60m1/min/ 1. 73 m2 was only 4 cases, and most of them were normal renal function. Stratified analysis of changes in eGFR with or without overt proteinuria showed that the changes in eGFR from the start at 52 weeks were those without the overt proteinuria (n=34, 0.6 ml/min/l. 73m2, 74.4 plus or minus 15.4
ml/min/l. 73m2 at the start) versus the overt proteinuria group (n = 7, -9.86 ml/min/l. 73m2, 74.0 plus or minus 7.9 ml/min/l. 73m2 at the start). It was significantly less compared to the
group without the overt proteinuria (p<0.01). The change in eGFR from the onset at week 104 was small without the overt proteinuria group (n=36), but did not reach to a significant difference (0.66 vs. overt proteinuria (+) group (n=6)), but did not reach to a significant difference (p=0.15). Changes in eGFR at 52 and 104 weeks were not correlated with initiation HbAIc or HbA1c decline. HbA1c at the start was 7.5%, significantly decreased at 52W and 104W (52W: 7.0%, 104W: 7.0%, p<0.01 vs. start, respectively). The weight reduction 52W was -3.6kg and this effect was maintained up to 104W. Diastolic blood pressure significantly decreased to 52W and 104W. Liver function improved significantly at 52W and 104W (p<0.01 vs. 0M, respectively) . lipid profile also
tended to be improved.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

06

Month

15

Day

Date of IRB

2017

Year

11

Month

17

Day

Anticipated trial start date

2018

Year

01

Month

04

Day

Last follow-up date

2022

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

11

Month

15

Day

Last modified on

2023

Year

04

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034211