fimasartan and Proteinuria

As angiotensin II type 1 receptor blockers (ARBs) may have different antiproteinuric effects in diabetic kidney disease (DKD), we ascertained the albuminuria-reducing effect of fimasartan and losartan in patients with DKD. This was a randomized, multicenter, double-blind, 4-parallel-group, dose-titration, phase III study designed to compare the efficacy of fimasartan and losartan in reducing albuminuria in patients with DKD (NCT02620306). The primary endpoint was the rate of change in albuminuria from baseline to week 24. A total of 341 patients were randomized to different groups. The urinary albumin-to-creatinine ratio (ACR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were not different between the fimasartan and losartan groups at baseline (ACR: 1376.84 vs. 1521.07 mg/gCr, SBP: 154.69 vs. 154.47 mmHg, DBP: 83.96 vs. 83.83 mmHg). However, ACR reduction was significantly larger in the fimasartan group than in the losartan group during the entire study period (% changes in the ACR at 4, 8, 12, and 24 weeks were -23.58, -33.06, -35.00, and -38.13 in the fimasartan group vs. -8.74, -10.17, -14.91, and -19.71 in the losartan group, p < 0.01, respectively). The superior antiproteinuric effect of fimasartan compared to losartan was still significant after adjustment for SBP levels. There were no significant differences in adverse events, including the incidences of estimated glomerular filtration decline and hyperkalemia. This study demonstrates that compared to losartan, fimasartan significantly reduces albuminuria in patients with DKD, even after adjustment for SBP and DBP.

Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus; Diabetic Nephropathies; Double-Blind Method; Humans; Hypertension; Losartan; Proteinuria; Renal Insufficiency, Chronic

Fimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes).. This study is a prospective, phase III, randomized, double-blind, active-controlled, non-inferiority, four-parallel group, dose-titration, multicenter trial. We recruit patients with hypertensive diabetic CKD with overt proteinuria. Participants will be randomized into four groups (1:1:1:1): fimasartan standard SBP control (SBP < 140 mmHg); fimasartan strict SBP control (SBP < 130 mmHg); losartan standard SBP control; and losartan strict SBP control. After 24 weeks, all individuals are treated with fimasartan for an additional 120 weeks in an open-label design, maintaining their assigned SBP control groups as randomized. The primary endpoint is the rate of change in proteinuria, which is assessed using the spot urine albumin-creatinine ratio at 24 weeks. The secondary endpoints are the cardiovascular and renal outcomes at 144 weeks compared between the strict SBP and standard SBP control groups.. The FANTASTIC is a clinical study to provide: (1) the reno-protective effect of fimasartan; and (2) the target BP to reduce adverse outcomes in hypertensive diabetic CKD with overt proteinuria.. Clinicaltrials.gov, NCT02620306. Registered on 1 December 2015.

Topics: Adult; Aged; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Clinical Trials, Phase III as Topic; Diabetes Complications; Diabetes Mellitus; Double-Blind Method; Endpoint Determination; Humans; Hypertension, Renal; Losartan; Middle Aged; Multicenter Studies as Topic; Nephritis; Prospective Studies; Proteinuria; Pyrimidines; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Tetrazoles