UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	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
Title of the study (Brief 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 (IDOL-EPOC Study )
Region	Japan

Condition
Condition	Type 2 DM complicated with high blood pressure
Classification by specialty	Cardiology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -but assessor(s) are blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
Name of lead principal investigator	Hiroyuki Kayano
Organization	Showa University School of Medicine
Division name	Division of Cardiology, Department of Medicine,
Address	1-5-8 Hatanaodai, Shinagawa-ku, Tokyo
TEL	03-3784-8000
Email	h-kayano@med.showa-u.ac.jp

Public contact
Name of contact person	Hiroki Takayama
Organization	Soiken Inc.
Division name	Clinical Study Support Division
Address	NBF Ogawamachi Building 4F, 1-3-1 Ogawamachi, Kanda, Chiyoda-ku, Tokyo
TEL	03-3295-1350
Homepage URL
Email	takayama@soiken.com

Sponsor
Institute	The Japan Society for Patient Reported Outcome
Institute
Department

Funding Source
Organization	1. AstraZeneca K.K. 2. Ono Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

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	2016 Year 08 Month 30 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2016 Year 08 Month 23 Day
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

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 08 Month 30 Day
Last modified on	2019 Year 03 Month 04 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000027461