Rationale and Design for Shiga Microalbuminuria Reduction Trial

Shiga University

Status and phase

Unknown

Phase 4

Conditions

Hypertension

Diabetes Mellitus

Albuminuria

Treatments

Drug: Amlodipine

Drug: Valsartan

Study type

Interventional

Funder types

Other

Identifiers

NCT00202618

SMART001

Details and patient eligibility

About

The purpose of this trial are to evaluate the reduction of urinary albumin excretion by an angiotensin receptor blocker (ARB), valsartan, in comparison with a calcium channel blocker (CCB), amlodipine, in Japanese hypertensive patients with type 2 diabetes mellitus and microalbuminuria under strict blood pressure control, and to compare the additional effects of an ARB or a CCB in combination with angiotensin-converting enzyme (ACE) inhibitor treatment.

Full description

Microalbuminuria in diabetic patients is an established risk marker for the progression of diabetic nephropathy and for cardiovascular mortality. Intervention trials have demonstrated that drugs that blockade the renin-angiotensin system can reduce microalbuminuria in Caucasian patients with type 2 diabetes mellitus and microalbuminuria, regardless of blood pressure level. However, it remains uncertain whether angiotensin receptor blockers or calcium channel blockers give a greater reduction of microalbuminuria. The Shiga Microalbuminuria Reduction Trial (SMART) is a prospective, multicentre, randomized, active-controlled, two-arm parallel treatment group comparison study aimed at evaluating reduction of microalbuminuria in 160 Japanese hypertensive patients with type 2 diabetes mellitus and microalbuminuria. The trial consists of an 8-week observation period for screening and washout, and a 24-week intervention period. After the observation period, patients are randomized to either amlodipine 5 mg once daily or valsartan 80 mg once daily as an initial dose. After four weeks, if patients cannot achieve the target blood pressure (<130/80 mmHg) with the initial dose of a study drug, doses are titrated up to amlodipine 10 mg once daily or valsartan 160 mg once daily. The primary endpoints are a change in the rate of urinary albumin excretion from baseline, a normalization of microalbuminuria, and a 50% reduction in urinary albumin excretion from baseline, which are compared between treatment groups. This study will provide additional data for the treatment of hypertension and microalbuminuria and has important health care implications for Japanese patients with type 2 diabetes.

Sex

All

Ages

35 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Hypertensive patient with type 2 diabetes
Microalbuminuria defined as a urinary albumin excretion of 30 to 300 mg/gCr

Exclusion criteria

Type 1 diabetes mellitus
Pregnant women and women of childbearing potential
Severe hypertension (> 180/110 mmHg), malignant hypertension, secondary hypertension
History of cardiovascular diseases in the preceding 6 months (including symptomatic heart failure, unstable angina, myocardial infarction, the performance of percutaneous transluminal coronary angioplasty [PTCA], or coronary artery bypass graft [CABG], severe arrhythmia, or second or third degree atrioventricular [AV] block)
History of clinically significant valvular disease (e.g., aortic stenosis, mitral insufficiency)
History of cerebral infarction, cerebral hemorrhage, or transient ischemic attack
Serum creatinine level >1.5 mg/dl
Persistent hematuria
Serum potassium > 5.6 mEq/L (hyperkalemia)
Severe hepatic disorder (e.g., hepatic failure, hepatic cirrhosis)
Complication of an allergy of potential clinical concern
Hypersensitivity to ARBs or CCBs
Gastrointestinal surgery or gastrointestinal disorders which could interfere with drug absorption
Autoimmune disease
Participation in any intervention trial within 3 months prior to the observation period
Patients who are unwilling or unable to comply with the trial protocol
Concomitant use of other ARBs, CCBs, or potassium-retaining diuretics