Comparison of effects between calcium channel blocker and diuretics in combination with angiotensin II receptor blocker on 24-h central blood pressure and vascular hemodynamic parameters in hypertensive patients: study design for a multicenter, double-blinded, active-controlled, phase 4, randomized trial

Abstract

Background: Hypertension is a risk factor for coronary heart disease and stroke, and is one of the leading causes of death. Although over a billion people are affected worldwide, only half of them receive adequate treatment. Current guidelines on antihypertensive treatment recommend combination therapy for patients not responding to monotherapy, but as the number of pills increase, patient compliance tends to decrease. As a result, fixed-dose combination drugs with different antihypertensive agents have been developed and widely used in recent years. CCBs have been shown to be better at reducing central blood pressure and arterial stiffness than diuretics. Recent studies have reported that central blood pressure and arterial stiffness are associated with cardiovascular outcomes. This trial aims to compare the efficacy of combination of calcium channel blocker (CCB) or thiazide diuretic with an angiotensin receptor blocker (ARB).

Methods: This is a multicenter, double-blinded, active-controlled, phase 4, randomized trial, comparing the antihypertensive effects of losartan/amlodipine and losartan/hydrochlorothiazide in patients unresponsive to treatment with losartan. The primary endpoint is changes in mean sitting systolic blood pressure (msSBP) after 4 weeks of treatment. Secondary endpoints are changes in msSBP, mean 24-h ambulatory mobile blood pressure, mean 24-h ambulatory mobile central SBP, mean 24-h ambulatory carotid-femoral pulse wave velocity, ambulatory augmentation index, and microalbuminuria/proteinuria after 20 weeks of treatment. The sample size will be 119 patients for each group in order to confer enough power to test for non-inferiority regarding the primary outcome.

Conclusion: The investigators aim to prove that combination of a CCB with ARB shows non-inferiority in lowering blood pressure compared with a combination of thiazide diuretic and ARB. We also hope to distinguish the subset of patients that are more responsive to certain types of combination drugs. The results of this study should aid physicians in selecting appropriate combination regimens to treat hypertension in certain populations.

Trial registration: ClinicalTrials.gov NCT02294539. Registered 12 November 2014.

Keywords: Angiotensin II receptor blocker; Arterial stiffness; Calcium channel blocker; Central blood pressure; Fixed dose combination; Hypertension.

Conflict of interest statement

Ethics approval and consent to participate

This trial will be performed in accordance with the declaration of Helsinki. All investigators will be required to obtain approval from the institutional review boards (IRB) from each participating center. All patients will sign a written consent form approved by the IRB. The study is also in accordance to the Korean good clinical practice (KGCP) and the international conference on harmonization-good clinical practice (ICH-GCP). (Consent for publication

Although the manuscript does not involve any clinical data, consent will be obtained for the data to be published at the time of recruitment into the study.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Study design