UMIN-CTR Clinical Trial

Public title

Impact of Dapagliflozin on Left ventricular hemodynamics and Exercise-induced Pulmonary hypertension evaluated by echocardiography in patients with type 2 diabetes; an open-label prospective randomized controlled trial

Acronym

Impact of Dapagliflozin on Left ventricular hemodynamics and Exercise-induced Pulmonary hypertension evaluated by echocardiography in patients with type 2 diabetes; an open-label prospective randomized controlled trial (IDOL-EPOC Study )

Scientific Title

Impact of Dapagliflozin on Left ventricular hemodynamics and Exercise-induced Pulmonary hypertension evaluated by echocardiography in patients with type 2 diabetes; an open-label prospective randomized controlled trial

Scientific Title:Acronym

Impact of Dapagliflozin on Left ventricular hemodynamics and Exercise-induced Pulmonary hypertension evaluated by echocardiography in patients with type 2 diabetes; an open-label prospective randomized controlled trial (IDOL-EPOC Study )

Region

Japan

Condition

Type 2 DM complicated with high blood pressure

Classification by specialty

Cardiology

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To study the cardioprotective efficacy of dapagliflozin by comparing it with conventional antidiabetic agents in type 2 diabetic patients with hypertension

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The amount and percentage change in right ventricular systolic pressure (PASP) under exercise stress between the baseline and week 24

Key secondary outcomes

1. Measurement at each observation point, and the amount and percentage change in right ventricular systolic pressure (PASP) under exercise stress at the observation week 6

Measurement and amount and percentage change from the baseline to each observation point for the following parameters:
2. Left ventricular ejection fraction (EF; %) as contractility
3. Left ventricular diastolic performance [E/A, Dec-time, and tissue Doppler echocardiography (e')]
4. Left atrial pressure (E/e')
5. Right ventricular systolic pressure as right heart function
6. Exercise tolerance measured during cardiopulmonary exercise testing (minute ventilation volume, carbon dioxide excretion, oxygen intake at peak and anaerobic metabolic thresholds)
7. Blood pressure measured at home (early morning blood pressure measured immediately before starting the administration and 2-week mean of blood pressure measured before sleep)
8. CAVI value
9. Body weight, abdominal circumference, and body composition
10. Amount of physical activity
11. Vital signs and general blood/urine tests
12. Special blood/urine tests
13. Incidence of pulmonary hypertension (50 mmHg or higher at rest, or 60 mmHg or higher with load) before and after exercise load (within case comparison between time points during exercise load should be made using data obtained with the same load level)
14. Incidence of hypoglycemia
15. Low blood pressure incidence
16. Incidence of abnormal electrolyte levels (low Na and K)
17. Incidence of other adverse events

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

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Group A: Administer dapagliflozin
Dapagliflozin is administered in addition to oral hypoglycemic agents that are in-use at the time of registration to this study, and continue to the week 24.
Dapagliflozin is initiated at a dose of 5 mg, and the dose is not increased until the week 6 observation point.
Dapagliflozin shall be taken once a day after breakfast.

Interventions/Control_2

Group B: Conventional treatment (adding any OHAs excluding SGLT2)
Only one type of hypoglycemic agent, other than insulin, GLP-1 agonists, and SGLT2*, is administered at the following dose in addition to oral hypoglycemic agents that are in-use at the time of registration to this study (no dose increase of a drug that is already in-use is allowed), and continue the medications until the week 24. The drug to be added shall be used within the scope of insurance coverage.
(Intervention drug, initial dose)
Biguanides, 750-1500 mg/day
Thiazolidines, 15 mg/day
There are no restrictions set for other hypoglycemic agents

Although no restrictions are set on the frequency of doses given per day, the dosage will not be increased until the week 6 observation (the initial dose will be maintained).

*Also, combination drugs are not allowed.

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

80

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients who meet all of the following criteria are included in this study.
1. Type 2 diabetic patients with HbA1c 7.0% to 9.0%
2. Patients who have been taking 1-3 different antidiabetic agents (oral hypoglycemic drugs) for at least12 weeks before consenting to study participation
3. Patients who were 20-year old or older, and younger than 80-year old at the time of consent
4. Patients with stage-I hypertension (early morning systolic blood pressure measured at home is 135 mmHg or higher and below 155 mmHg, or systolic blood pressure measured at office is 140 mmHg or higher and below 160 mmHg), stage-II hypertension (early morning systolic blood pressure measured at home is 155 mmHg or higher and below 175 mmHg, or systolic blood pressure measured at office is 160 mmHg or higher and below 180 mmHg), or an annually averaged systolic blood pressure measured at office is 140 mmHg or higher and below 160 mmHg, or currently on antihypertensive medication and with ischemic heart disease
5. Patients who can consent in writing

Key exclusion criteria

Patients who fall into one or more of the following criteria are excluded from participating in the study.
1. Patients requiring a legally acceptable representative
2. Patients with type 1 diabetes
3. Patients who have received an SGLT2 inhibitor, subcutaneous injection of insulin, or subcutaneous injection of glucagon-like-peptide-1 agonist within 12 weeks before consenting to study participation
4. Patients with the stage-III hypertension (early morning systolic blood pressure measured at home is 175 mmHg or higher, or systolic blood pressure measured at office is 180 mmHg or higher)
5. Patients with chronic respiratory disease that needs medical treatment
6. Patients with pulmonary hypertension
7. Patients with severe renal failure (GFR is below 45 mL/min/1.73 m2)
8. Patients with an infectious disease or undergoing cancer treatment
9. Patients who have undergone surgery or catheter treatment within a year before consenting to study participation
10. Patients who are or may be pregnant
11. Patients who are drug addicted or alcohol dependent
12. Patients with NYHA III-IV heart failure
13. Patients considered inappropriate by their attending investigators

Target sample size

78

Name of lead principal investigator

1st name
Middle name
Last name	Hiroyuki Kayano

Organization

Showa University School of Medicine

Division name

Division of Cardiology, Department of Medicine,

Zip code

Address

1-5-8 Hatanaodai, Shinagawa-ku, Tokyo

TEL

03-3784-8000

Email

h-kayano@med.showa-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Hiroki Takayama

Organization

Soiken Inc.

Division name

Clinical Study Support Division

Zip code

Address

NBF Ogawamachi Building 4F, 1-3-1 Ogawamachi, Kanda, Chiyoda-ku, Tokyo

TEL

03-3295-1350

Homepage URL

Email

takayama@soiken.com

Institute

The Japan Society for Patient Reported Outcome

Institute

Department

Personal name

Organization

1. AstraZeneca K.K.
2. Ono Pharmaceutical Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

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

2016

Year

08

Month

30

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2016

Year

08

Month

23

Day

Date of IRB

Anticipated trial start date

2016

Year

09

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

08

Month

30

Day

Last modified on

2019

Year

03

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027461