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Randomized Controlled Trial
. 2014 Jun 21;11(9):897-904.
doi: 10.7150/ijms.9026. eCollection 2014.

Comparison of the antialbuminuric effects of benidipine and hydrochlorothiazide in Renin-Angiotensin System (RAS) inhibitor-treated hypertensive patients with albuminuria: the COSMO-CKD (COmbination Strategy on Renal Function of Benidipine or Diuretics TreatMent with RAS inhibitOrs in a Chronic Kidney Disease Hypertensive Population) study

Katsuyuki Ando  1 , Kosaku Nitta  2 , Hiromi Rakugi  3 , Yoshiki Nishizawa  4 , Hitoshi Yokoyama  5 , Takeshi Nakanishi  6 , Naoki Kashihara  7 , Kimio Tomita  8 , Masaomi Nangaku  9 , Katsutoshi Takahashi  9 , Masashi Isshiki  9 , Tatsuo Shimosawa  10 , Toshiro Fujita  11
Affiliations
Randomized Controlled Trial

Comparison of the antialbuminuric effects of benidipine and hydrochlorothiazide in Renin-Angiotensin System (RAS) inhibitor-treated hypertensive patients with albuminuria: the COSMO-CKD (COmbination Strategy on Renal Function of Benidipine or Diuretics TreatMent with RAS inhibitOrs in a Chronic Kidney Disease Hypertensive Population) study

Katsuyuki Ando et al. Int J Med Sci. .

Abstract

Objective: This study evaluated the non-inferiority of renoprotection afforded by benidipine versus hydrochlorothiazide in hypertensive patients with chronic kidney disease (CKD).

Methods: In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of benidipine and hydrochlorothiazide were examined in renin-angiotensin system (RAS) inhibitor-treated patients with blood pressure (BP) readings of ≥ 130/80 mmHg and ≤ 180/110 mmHg, a urinary albumin to creatinine ratio (UACR) of ≥ 300 mg/g, and an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73m(2). Patients received benidipine (n = 176, final dose: 4.8 mg/day) or hydrochlorothiazide (n = 170, 8.2 mg/day) for 12 months.

Results: Benidipine and hydrochlorothiazide exerted similar BP- and eGFR-decreasing actions. The UACR values for benidipine and hydrochlorothiazide were 930.8 (95% confidence interval: 826.1, 1048.7) and 883.1 (781.7, 997.7) mg/g at baseline, respectively. These values were reduced to 790.0 (668.1, 934.2) and 448.5 (372.9, 539.4) mg/g at last observation carried forward (LOCF) visits. The non-inferiority of benidipine versus hydrochlorothiazide was not demonstrated (benidipine/hydrochlorothiazide ratio of LOCF value adjusted for baseline: 1.67 (1.40, 1.99)).

Conclusions: The present study failed to demonstrate the non-inferiority of the antialbuminuric effect of benidipine relative to that of hydrochlorothiazide in RAS inhibitor-treated hypertensive patients with macroalbuminuria.

Keywords: L-/N-/T-type calcium channel blocker, thiazide diuretic, urinary albumin.; chronic kidney disease, hypertension, renin-angiotensin system inhibitor.

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Conflict of interest statement

Competing Interests: The first author (K.A.) is endowed by Daiichi-Sankyo, Co., Ltd. (Tokyo, Japan). The last author (T.F.) is endowed by Mochida Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ltd., Kyowa Hakko Kirin Co., Ltd., MSD Co., Ltd., Toray Industries, Inc., and Terumo Cooperation (all in Tokyo, Japan).

Figures

Figure 1
Figure 1
Study protocol. BP, blood pressure; CCB, calcium channel blocker; RAS, renin-angiotensin system.
Figure 2
Figure 2
Changes in the urinary albumin/creatinine ratio (UACR). a) The decrease in UACR was greater in the hydrochlorothiazide group than in the benidipine group, as indicated by the endpoint/baseline ratio of the UACR for each drug. Data (black and white circles) are given as the mean ± the standard deviation (SD). LOCF, last observation carried forward. * The endpoint/baseline ratio of the UACR for each drug is given as the mean (95% confidence interval). b) The endpoint/baseline data are given as the ratio of the benidipine arm/hydrochlorothiazide arm (mean and 95% confidence interval). The non-inferiority of benidipine was not demonstrated.
Figure 3
Figure 3
Changes in serum creatinine (a) and estimated glomerular filtration rate (eGFR) (b). Data (black and white circles) are given as the mean ± the standard deviation (SD). LOCF, last observation carried forward. * The endpoint/baseline ratios for benidipine and hydrochlorothiazide are each given as the mean (95% confidence interval).
Figure 4
Figure 4
Changes in systolic and diastolic blood pressure (BP). Data are given as the mean ± the standard deviation (SD). LOCF, last observation carried forward. * Changes in the BP from the baseline to the endpoint are shown as the mean (95% confidence interval).
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