DAPPER study

JRCT ID: jRCTs051180135

Registered date:18/03/2019

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Type 2 Diabetes Mellitus patients with Chronic Heart Failure
• Date of first enrollment: 12/05/2017
• Target sample size: 288
• Study type: Interventional

Intervention(s)

dapagliflozin, 5 mg or 10 mg, 2 years observation

anti-diabetic drugs except for SGLT-2 inhibitors, 2 years observation

Outcome(s)

• Primary Outcome: The changes in the urine albumin-to-creatinine ratio (UACR) from the baseline after a 2-year observation

Secondary Outcome

(1) The proportion of the number of patients presenting with an albuminuria category shift in each group (dapagliflozingroup and control group)
Improvement test
A shift to a better category
Prevention test
No shift to a worse category
Categories
Category 1 (less than 30 mg/g Cr)
Category 2 (from 30 to 299 mg/g Cr)
Category 3 (more than 300 mg/g Cr)
(2) Changes of eGFR during a 2-year period
(3) The proportion of the number of patients presenting with an eGFR category shift in each group
Improvement test
A shift to a better category
Prevention test
No shift or a shift to a worse category
Categories
Category 1 (more than 90 ml/min/1.73m2)
Category 2 (from 89 to 60 ml/min/1.73m2)
Category 3 (from 59 to 45 ml/min/1.73m2)
(4) The changes of urinary kidney injury molecule-1 (KIM-1) from the baseline after a 2-year observation
(5) The changes in the plasma aldosterone concentration, plasma NT-proBNP concentration, serum FGF23 concentration,and plasma alpha-Klotho concentration from the baseline after a 2-year observation
(6) The composite endpoint, which is defined as CV death or hospitalization for CV events in a 2-year observation
(7) The composite endpoint, which is defined as CV death or the hospitalization for HF in a 2-year observation
(8) The onset of CV events in a 2-year observation
(9) Hospitalization for CV events in a 2-year observation
(10) Hospitalization for HF in a 2-year observation
(11) Death from all causes in a 2-year observation
(12) Hospitalization for all causes in a 2-year observation
(13) An additional change in prescriptions for HF in a 2-year observation
(14) The changes in echocardiographic parameters, including left ventricular end-diastolic and end-systolic dimensions, the left atrial volume index, left atrial dimension, (15) ejection fraction, and (16) fractional shortening from the baseline after a 2-year observation
(17) The category of the New York Heart Association (NYHA) classification in a 2-year observation
(18) The changes in echocardiographic parameters, including mitral peak E-wave (E) from the baseline after a 2-year observation
(19) The changes in echocardiographic parameters, including early diastolic mitral annular velocity by tissue doppler echocardiography (e' ) from the baseline after a 2-year observation
(20) The changes in echocardiographic parameters, including E/mitral peak A velocity (A) ratio from the baseline after a 2-year observation
(21) The changes in echocardiographic parameters, including E/e' ratio from the baseline after a 2-year observation
(22) The changes in echocardiographic parameters, including E velocity deceleration time from the baseline after a 2-year observation
(23) New-onset atrial fibrillation and/or atrial flutter in a 2-year observation

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1) Patients with type 2 diabetes at 20 years-old or older and less than or equal to 85 years-old at the time of informed consent
2) Patients necessary to start the treatment using anti-diabetic agent(s) or to change the anti-diabetic agent(s)
3) Patients with plasma HbA1C levels < 10% with or without anti-diabetic agent(s)
4) Patients who fall into any of the following items are defined as those with chronic heart failure:
1. NYHA Functional Class II, III or IV within 3 months before informed consent
2. Plasma BNP levels of 100 pg/mL or plasma NT-pro BNP levels of 400 pg/mL within 3 months before informed consent
3. previous diagnosis of heart failure that was treated including drug therapy.
5) The value of eGFR should be more than 45 ml/min/1.73m2
6) Agreement of written informed consent

Exclude criteria

1) Patients with insulin treatment
2) Patients with an allergic history of dapagliflozin
3) Patients with a history of severe diabetic ketoacidosis, diabetic coma or pre-coma
4) Patients using mechanical circulatory support devices
5) Patients waiting for heart transplant
6) Patients waiting for cardiac surgery
7) Patients who may easily show dehydration, including a history of dehydration, highly frequent change of diuretics, extreme thinness
8) Patients with hepatic dysfunction with AST or ALT 3-fold of upper limit of normal (ULN) at screening (However, if increased AST or ALT is determined to be attributable to cardiac diseases, patients do not meet this exclusion criterion as long as total bilirubin levels are < 3.0 mg/dL.)
9) Patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney
10) Patients in a serious clinical condition and who are expected to live for < 3 years
11) Patients with possible alcohol or drug abuse
12) Patients who are pregnant or possibly pregnant
13) Patients with breast feeding
14) Patients who have been enrolled in other clinical studies at the same time with this study (excluding observational studies such as registry studies)
15) Patients who are judged by the investigator or subinvestigators to be not suitable for participation in the study

Related Information

• Primary Sponsor: Yoshihara Fumiki
• Source(s) of Monetary Support: Astra Zeneka KK,Ono Pharmaceutical Co., Ltd.
• Secondary ID(s): UMIN000025102