Abstract
BackgroundThe efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone (diuretic) versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously. We plan to compare the efficacy and safety of S-amlodipine (CCB) plus chlorthalidone versus S-amlodipine plus telmisartan (ARB) combinations among hypertension patients unresponsive to amlodipine monotherapy.Methods/designThis study is a prospective, randomized, double-blind, multicenter, parallel, non-inferiority phase 4 study. Hypertension patients who have been treated with amlodipine (5 mg) or S-amlodipine (2.5 mg) monotherapy for ≥2 weeks and whose mean diastolic blood pressure (DBP) is greater than 90 mmHg will be randomized to either S-amlodipine (2.5 mg) plus chlorthalidone (25 mg) or S-amlodipine (2.5 mg) plus telmisartan (40 mg) therapy. The primary efficacy endpoint is mean sitting DBP change after 12 weeks of treatment. The study objective is to prove the non-inferiority of the former combination (test drug) as compared to the latter one (control) with a non-inferiority margin of 3 mmHg in mean DBP change. The secondary endpoints are 6-week DBP change, 6- and 12-week sitting systolic BP (SBP) change, and the attainment of the target BP (SBP < 140 mmHg or DBP < 90 mmHg). Urine albumin, albumin/creatinine ratio (ACR), pulse wave velocity, central BP, 24-h ambulatory BP monitoring, and body fluid composition analysis will be performed at each hospital’s discretion. The sample size was estimated as 170 in total with 1:1 randomization.DiscussionThis is the first study comparing the efficacy of a CCB plus chlorthalidone versus a CCB plus an ARB in patients who are not responding to CCB single therapy. The study result will help clinicians to choose between chlorthalidone and telmisartan in CCB-unresponsive patients.Trial registrationClinicalTrials.gov, NCT03226340. Registered on 2 December 2015.
Highlights
The efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously
This is the first study comparing the efficacy of a CCB plus chlorthalidone versus a CCB plus an ARB in patients who are not responding to CCB single therapy
This study compares two regimens of combination therapy in a head-to-head manner to demonstrate the non-inferiority of CCB + diuretic in blood pressure (BP)-lowering efficacy and safety compared to CCB + ARB as a combination therapy
Summary
Multiple drug therapy ought to be considered by physicians to manage the BP adequately in hypertension patients. We propose to investigate the change in BP within a short period, instead of long-term clinical outcomes, we are certain that the results of our study will clarify existing knowledge on the efficacy and safety of CCB + diuretic and will provide clinicians with another option for treating hypertension in patients who do not respond adequately to treatment with a single agent Other ancillary parameters, such as pulse wave velocity, central blood pressure, 24-h ambulatory BP monitoring, and body fluid composition analysis, in some patients will give additional insight into the change in aortic stiffness, BP control throughout the day, and effect on edema, which is the major adverse effect of CCBs. If a meaningful difference is observed between the two combinations, it will allow physicians to better choose drugs in combination, especially for patients experiencing adverse effects of the currently used therapy and in special clinical situations, such as heart failure.
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