A multicenter, parallel randomized,open label trial of two groups
N/A
1.Type 2 diabetes (outpatient)
2.Age at informed consent: 20 to 79 years old
3.Hypertension treated with a fixed dose of ARB or ACEI for more than 3 months at informed consent
4.Urinary albumin-to-creatinine ratios (UACR) in the first morning urine: >= 45 mg/gCr and <1000 mg/gCr at the last two time points before registration
5.Office blood-pressure (seating position): 130 mmHg =< systolic-blood-pressure < 150 mmHg and 50 mmHg =< diastolic blood pressure < 95 mmHg at the last two time points before registration
1.Type 1 diabetes
2.History of treatment by MR antagonist (potassium sparing diuretics) within one year before informed consent.
3.History of treatment by renin inhibitor within three months before informed consent.
4.HbA1c: >= 8.4% (NGSP) at the last before registration.
5.BMI: >= 35 at the last before registration
6.Renovascular hypertension, bilateral or unilateral renal artery stenosis, renal artery stenosis with unilateral kidney.
7.Progressive decline of renal function and it may result in an end-stage renal disease during the study.
8.eGFR: <45 mL/min/1.73 m2 at the last before registration
9.Serum potassium: >=5.0 mEq/L at the last before registration
10.Uric acid: >=9.0 mg/dl at the last before registration
11.History of acute coronary syndrome (ACS), percutaneous coronary-arteries intervention (PCI), coronary-artery bypass surgery (CABG), stroke, the transient ischemic attack (TIA) and revascularization of the carotid artery or the peripheral artery within 6 months before registration
12.Heart failure classified into NYHA III or IV.
13.The malignant tumor.
14.Serious liver disease (hepatic insufficiency, liver cirrhosis, etc.).
15.Pregnancy, possible to be pregnant or willing to be pregnant and lactation.
16.Patients with contraindication to study drugs.
17.Patients with a plan of treatment by tacrolimus or mitotan
18.Patients considered to be inappropriate by investigator
20age old over
79age old under
Both
Type 2 Diabetes
investigational material(s)
Generic name etc : Spironolactone
INN of investigational material : Spironolactone
Therapeutic category code : 213 Diuretics
Dosage and Administration for Investigational material : Oral
Ratio of paient met with either of the followings;
- In case of '300 mg/gCr =< UACR < 1000 mg/gCr at run-in period', both UACRs at two time points of the end of treatment are less than 300 mg/gCr and decrease by >=30% compared to baseline.
- In case of '45 mg/gCr =< UACR < 300 mg/gCr at run-in period', both UACRs at two time points of the end of treatment are less than 30 mg/gCr.
-Both UACRs at two time points of the end of treatment decrease by >=50% compares to baseline.
Odds ratio with 95% confidence interval and P value for the standard anti-hypertensive therapy plus spironolactone group compared with the standard anti-hypertensive therapy group are estimated by logistic regression.
1. Ratio of paient met with either of the followings;
-In case of '300 mg/gCr =< UACR < 1000 mg/gCr at run-in period', both UACRs at two time points of the end of treatment are less than 300 mg/gCr and decrease by >= 30% compared to baseline.
-In case of '45 mg/gCr =< UACR < 300 mg/gCr at run-in period', both UACRs at two time points of the end of treatment are less than 30 mg/gCr.
2. Ratio of patient met with the following;
Both UACRs at two time points of the end of treatment decrease by >= 50% compared to baseline.
3. Normalization ratio of albuminuria at the end of treatment period
4. Progression ratio of diabetic nephropathy stage at the end of treatment period
5. Occurrence of renal composite end point (doubling of serum creatinine level, end-stage renal disease (ESRD), or death)
6. UACR change and transition from baseline
7. eGFR change and transition from baseline
1,2,3,4,5 : Odds ratio with 95% confidence interval and P value for the standard anti-hypertensive therapy plus spironolactone group compared with the standard anti-hypertensive therapy group are estimated by logistic regression.
6: Geometric mean and percent change from baseline are calculated and plotted.
7 : Summary statistics are calculated and plotted.
