UMIN-CTR Clinical Trial

Public title

Effects of Long-term Dapagliflozin Treatment on Hemorheology, Leukocyte Activation and Oxidative Stress

Acronym

Effects of Long-term Dapagliflozin Treatment on Hemorheology, Leukocyte Activation and Oxidative Stress

Scientific Title

Effects of Long-term Dapagliflozin Treatment on Hemorheology, Leukocyte Activation and Oxidative Stress

Scientific Title:Acronym

Effects of Long-term Dapagliflozin Treatment on Hemorheology, Leukocyte Activation and Oxidative Stress

Region

Japan

Condition

Type 2 diabetes mellitus

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To determine the hypothesis that 16 weeks of treatment with dapagliflozin is, despite mildly elevated haematocrit, noninferior in terms of hemorheology to the non-dapagliflozin treatment group (conventional treatment group), and to furthermore study the effect on leukocyte activation and oxidative stress.

Basic objectives2

Pharmacodynamics

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Whole blood transit time (0.1 mL) and the difference from baseline at 16 weeks after enrollment, as assessed using the microchannel array flow analyzer (MC-FAN) equipped with BK 7-7-7D chip

Key secondary outcomes

Blood samples at 8 and 16 weeks after enrollment (whole blood transit time (0.1 mL) and difference from baseline as determined using the MC-FAN with DKAMCM1-60-7-4.5D, leukocyte activation (adhesive leukocyte count as determined using the MC-FAN with DKAMCM1-60-7-4.5D , difference between whole blood transit time in heparin (5% vol) blood samples and whole blood transit time in EDTA-2Na + heparin blood samples as determined using the DKAMCM1-60-7-4.5D), CBC, lipid system, hsCRP, serum creatinine, hydroperoxide levels as serum levels of reactive oxygen metabolite (d-ROM) and antioxidant potencial as determined by BAP test using F.R.E.E. carpe diem (Diacron srl, Grosseto, Italy) and urine samples (albuminuria assay); whole blood transit time (0.1 mL) and difference from baseline as determined using the MC-FAN 7-7-7D chip at 8 weeks after enrollment; and percentage in which whole blood transit time (0.1 mL) did not increase =>6.0sec(15%), as determined using MC-FAN at 8 and 16 weeks after enrollment

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Dapagliflozin treatment group: Oral dapagliflozin 5 mg/day in combination with standard therapy (the dapagliflozin dose can be increased to 10 mg in subjects with inadequate response to 5 mg)

Interventions/Control_2

Non-dapagliflozin treatment group: Optimal diabetes treatment other than an SGLT2 inhibitor in combination with standard therapy

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

75

years-old

>=

Gender

Male and Female

Key inclusion criteria

(a) 20 to 75 years of age at informed consent
(b) Type 2 diabetes mellitus patient, with HbA1c>7.0%
(c) Diabetic nephropathy stage <=3
(d) Patients visiting the hospital on an outpatient basis for diabetic therapy, who provide written informed consent

Key exclusion criteria

(a) Patients with type 1 diabetes mellitus
(b) Patients with a medical history of hypersensitivity to any of the ingredients of dapagliflozin
(c) Patients with severe ketosis or diabetic coma or pre-coma
(d) Patients who have severe infection, are pre- or postoperative, or have sustained serious trauma
(e) Patients with severe impaired liver function
(f) Patients who are susceptible to dehydration
(g) Patients with urinary tract infection or genital infection
(h) Patients with a history of cerebrovascular disease within the last 3 months
(i) Women who are pregnant or breastfeeding or who may be pregnant
(j) Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 mL
(k) Patients on warfarin or a novel oral anticoagulant (NOAC) (dabigatran, rivaroxaban, edoxaban, or apixaban)
(l) Current smokers
(m) Patients otherwise deemed to be unsuitable for the clinical study by investigators

Target sample size

90

Name of lead principal investigator

1st name	Takanori
Middle name
Last name	Yasu

Organization

Dokkyo Medical University Nikko Medical Center

Division name

Deparment of Cardiovascular Medicine and Nephrology

Zip code

321-2593

Address

632 Takatoku, Nikko City, Tochigi

TEL

0288-76-1515

Email

tyasu@dokkyomed.ac.jp

Name of contact person

1st name	Akiko
Middle name
Last name	Niijima

Organization

Dokkyo Medical University Nikko Medical Center

Division name

Clinical Study Support Center

Zip code

321-2593

Address

632 Takatoku, Nikko City, Tochigi

TEL

0288-76-1515

Homepage URL

Email

aniijima@dokkyomed.ac.jp

Institute

Dokkyo Medical University Nikko Medical Center
Department of Clinical Study Support Center

Institute

Department

Personal name

Organization

ONO Pharmaceutical CO.,LTD.
AstraZeneca K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Department of Cardiovascular Medicine,Nephrology and Neurology,University of the Ryukyus.
Yokokawa Clinic

Name of secondary funder(s)

Organization

Dokkyo Medical University Nikko Medical Center IRB

Address

632 Takatoku, Nikko City, Tochigi

Tel

0288-76-1515

Email

rinshokenkyu@dokkyomed.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

獨協医科大学日光医療センター

Date of disclosure of the study information

2017

Year

02

Month

01

Day

URL releasing protocol

https://center6.umin.ac.jp/cgi-bin/ctr/ctr_up_reg_f7.cgi

Publication of results

Published

URL related to results and publications

https://center6.umin.ac.jp/cgi-bin/ctr/ctr_up_reg_f7.cgi

Number of participants that the trial has enrolled

90

Results

In type 2 diabetes patients, 16 weeks of Dapagliflozin administration increased hematocrit by approximately 2%, but blood fluidity was proven to be non-inferior to conventional treatment groups.
Dapagliflozin group Control group
Before (mean +- SD) 41.8 +- 6.1 seconds 40.5 +- 3.0 seconds
After 16 weeks 43.4 +- 6.8 seconds 39.9 +- 3.8 seconds
Difference from baseline (95% CI) 1.4 seconds (0.01, 2.79 -0.45 seconds (-1.50, 0.55)

Results date posted

2019

Year

07

Month

24

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The subject of the relevant clinical research
Type 2 diabetes mellitus patient,with HbA1c>7.0% Diabetic nephropathy stage<=3 Age 20 to 75 at the time of consent acquisition
Comparison group
Assigned to Dapagliflozin administration group and non-administration group
Dapagliflozin treatment is a combination treatment of Dapagliflozin 5mg / day orally with basic treatment (can be increased to 10mg for cases with insufficient effect)
Non-administration group is treated with basic treatment combined with appropriate diabetes treatment other than SGLT2 inhibitor

Participant flow

2017/4/26　First person consent acquisition / examination start
2017/3/31　Number of consent holders: 43 Number of consent withdrawals: 1
2018/11/28　90th (final) consent obtained
2019/3/20 End of observation　Consent withdrawal number of people 5 Discontinuance number of people 4

Adverse events

Disease reports 1 case　Other adverse events 9

Outcome measures

(1) Primary endpoint
Whole blood transit time (0.1 ml) using MC-FAN BK 7-7-7D chip at 16 weeks after the start of registration and their difference from baseline

(2) Secondary endpoint
Blood collection at 8 and 16 weeks after the start of registration (whole blood transit time (0.1 ml) using MC-FAN DKAMCM1-60-7-4.5D and their difference from baseline, leukocyte activation (leukocyte adhesion number using DKAMCM1-60-7-4.5D, difference between whole blood transit time of heparin (5% vol) blood collection and whole blood transit time of EDTA-2Na + heparin blood collection using DKAMCM1-60-7-4.5D), CBC, lipid system, hsCRP, serum creatinine, oxidative stress level by d-ROMs test, antioxidant power by BAP test, urine collection (quantitative albuminuria), MC-FAN 7-7-7D at 8 weeks after the start of registration Whole blood transit time (0.1 ml) using chip and its difference from baseline, and the proportion of patients whose whole blood transit time (0.1 ml) using MC-FAN did not increase by 6 seconds (15%) from the baseline value at 8 and 16 weeks after the start of enrollment

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

01

Month

19

Day

Date of IRB

2016

Year

11

Month

26

Day

Anticipated trial start date

2017

Year

02

Month

20

Day

Last follow-up date

2019

Year

03

Month

20

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

01

Month

20

Day

Last modified on

2024

Year

11

Month

22

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029107