Effect of Fimasartan on Extended RAS and Vascular Functions in Patients With Type 2 Diabetes and Hypertension

Phase 4

Recruiting

Conditions: Atherosclerosis
Diabetes Mellitus, Type 2
Renin Hypertension
Hypertension

Brief Summary: In this study, we will assess the change of extended renin-angiotensin system including serum ACE-2 and angiotensin(1-7) levels and subclinical atherosclerosis after using fimasartan (an ARB), compared to amlodipine in hypertensive patients with T2DM.

Detailed Description: Several clinical trials aimed at studying the benefits of RAS blockade in the diabetic complications. HOPE, RENAAL, IRMA2, IDNT, ONTARGET studies proved that ACE inhibitors or ARBs reduced the risk of diabetic complications.

Recent studies proved that fimasartan, one of the ARBs, stabilizes the activity of renin-angiotensin system. However, understanding the change in concentration of serum ACE, ACE-2, angiotensin(1-7), and angiotensin-II should help clinicians select more appropriate drug between ACE inhibitors and ARBs with clear evidence. Moreover, since RAS antagonists are the first-line drugs for antihypertensive therapy in patients with T2DM, it is meaningful to understand the change of RAS-related factors in serum after using the drugs.

Recruitment & Eligibility

Inclusion Criteria

≥ 30 years old
Type 2 diabetes by American Diabetes Association criteria
HbA1c: 6.5% ≤ - < 10.0%
Systolic blood pressure: 140 ≤ - < 180 mmHg or Diastolic blood pressure: 85 ≤ - < 110 mmHg
Statin (-) or no change in low to moderate intensity statin [14] dose in recent 3 months

Exclusion Criteria

Contraindication of fimasartan or amlodipine
History of RAS inhibitors (ACE inhibitors or ARBs) or calcium channel blockers in the previous 3 months
Pregnant women, women with potential of pregnancy not using adequate contraception method as evaluated by the investigator, lactating women
Type 1 diabetes or diabetes secondary to chronic pancreatitis or to pancreatectomy
Confirmed cardiovascular disease (acute coronary syndrome, stroke, or transient ischemic attack) within 3 months of screening
Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT > 3-fold the upper limit of normal)
Chronic kidney disease (serum creatinine > 2.0 mg/dL)
Hyperkalemia serum potassium >5.0 mEq/L
Any previous cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer with appropriate treatment) except thyroid cancer or carcinoma in situ

Arm && Interventions

Group	Intervention	Description
Fimasartan	Fimasartan	- Fimasartan group: Fimasartan, 60 mg once a day, oral administration
Amlodipine	Fimasartan	- Comparator group: Amlodipine, 5 mg once a day, oral administration

Primary Outcome Measures

Name	Time	Method
Angiotensin(1-7)	12 weeks	Changes of serum angiotensin(1-7) at week 12 from baseline

Secondary Outcome Measures

Name	Time	Method
Renin	12 weeks	Change in renin from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
angiotensin	12 weeks	Change in angiotensin from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
atherosclerosis	12 weeks	Change in atherosclerosis from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
Muscle mass	12 weeks	Change in muscle mass from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
HbA1c	12 weeks	Change in HbA1c from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
Blood pressure	12 weeks	Change in blood pressure from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
ACE-2	12 weeks	Change in ACE-2 from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
ACE	12 weeks	Change in ACE from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24
Fat mass	12 weeks	Change in fat mass from baseline to week 12 Change in blood pressure from baseline to week 24 Change in blood pressure from baseline to week 24

Locations (1): Seoul National University Bundang Hospital
🇰🇷
Seongnam, Gyeonggi, Korea, Republic of