5 mg; a half of the optimal dose) (LOS/HCTZ) is thus worth evaluating in terms of BP lowering potency and avoiding side effects. In the present study, we made an attempt to evaluate the clinical

benefit of a single-tablet formulation of LOS/HCTZ, by conducting a multicenter observational trial, the Jikei Optimal Antihypertensive Treatment (JOINT) study in uncontrolled hypertensive patients. Methods Study subjects MDV3100 Eligible patients were men and women between 20 and 75 years of age with essential hypertension and those with CKD with hypertension. Ethnic extraction of all participants was Japanese with all four biological grandparents born in Japan and of Japanese descent. The inclusion criteria were outpatients whose BP was more than 130/80 mmHg despite the antihypertensive agents prescribed for more than 3 months prior to study entry. The exclusion criteria were patients whose CB-839 in vivo serum creatinine (Cr) concentration exceeded 220 μmol/L (compatible with CKD stage 5), those with liver dysfunction (defined

as an elevation of aspartate aminotransferase/alanine aminotransferase 3 times higher than the upper normal limit), pregnant, expecting, or lactating women, CKD patients with massive proteinuria of nephrotic range (defined as a daily protein excretion of 3 g/day or more), and patients whose doctor in charge judged it inappropriate to enroll. Study protocol All institutions received prior ethics committee and or institutional review board approval, and the trial was conducted in accordance with the AZD3965 purchase principles of Good Clinical Practice and the ethical principles of the concurrent Declaration of Helsinki which also protected the privacy of the patients. All patients gave written informed consent before study enrollment. The JOINT

was a multicenter observational self-controlled study to evaluate the antihypertensive effect of a fixed-dose combination formulation of LOS/HCTZ (Clinical trial Number by UMIN 000001950). The study was conducted at 28 centers and clinics for the JOINT study group (“Appendix”) in the vicinity of Tokyo, Japan. Patients were previously treated with either one or more antihypertensive agents on an outpatient basis. The protocol for the administration of LOS/HCTZ was the following. If the patient was being treated with either ARB or calcium channel blocker (CCB) alone or together, LOS/HCTZ was substituted for either Guanylate cyclase 2C drug or the combination. If the patient was being treated with three drugs including RAS inhibitors, the RAS inhibitor was switched to LOS/HCTZ. In all of the protocol patterns, LOS/HCTZ was administered once a day in the morning. Advices on life-style modification plan were carried out throughout the study. Namely, from the run-in and the observation period, the patients were required to maintain a daily salt intake of 6 g or less. A protein restriction of 0.6–0.8 g/kg/day was also required when the patient’s CCr was below 30 mL/min/1.73 m2.