title: Add-on effect of hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension uncontrolled with losartan 50 mg and amlodipine 5 mg.
abstract: This study assessed the antihypertensive efficacy of a triple combination, fixed-dose therapy of losartan 50 mg (L50)/hydrochlorothiazide 12.5 mg (H12.5)/amlodipine 5 mg (A5) versus co-administration of L50 plus A5 (L50+A5) in Japanese subjects with uncontrolled essential hypertension. Initially, all subjects received single-blind treatment with L50+A5 for 8 weeks. Subjects whose blood pressure (BP) remained stable within pre-specified limits during the last 4 weeks of L50+A5 administration were randomized (n =3 27) to double-blind treatment with L50/H12.5/A5 or L50+A5 for 8 weeks. Primary and secondary efficacy endpoints were mean change from baseline to Week 8 in trough diastolic BP (DBP) and trough systolic BP (SBP), respectively. Safety was assessed throughout the study. The treatment difference for L50/H12.5/A5 versus L50+A5 in mean change from baseline in DBP at Week 8 was -1.1 mm Hg (95% confidence interval (CI) -2.7, 0.6; P = 0.205). However, the treatment difference in mean change from baseline in SBP at Week 8 was -3.2 mm Hg (95% CI: -5.7, -0.8; P=0.011). A chance imbalance in the change in DBP before randomization between groups was identified in a post-hoc analysis as a major reason for the smaller-than-expected difference in DBP between groups. The overall safety profile was generally similar between groups. In conclusion, treatment with L50/H12.5/A5 for 8 weeks did not demonstrate a significant difference in DBP reduction, but demonstrated a nominally significant difference in SBP reduction, compared with L50+A5. L50/H12.5/A5 was well tolerated. (ClinicalTrials.gov identifier NCT01302691.).
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
authors.affiliation: Hypertension Center, Steel Memorial Yawata Hospital, Kitakyushu, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsuchihashi
authors.affiliation: Department of Internal Medicine and Cardiology, Shin-Oyama City Hospital, Oyama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Numaguchi
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Nishida
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shirakawa
authors.affiliation: MSD K.K., Tokyo, Japan.
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Kenji P
authors.initials: KP
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy*; D007564:Japan; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017311:Amlodipine; D019808:Losartan