S-amlodipine plus chlorthalidone vs. S-amlodipine plus telmisartan in hypertensive patients unresponsive to amlodipine monotherapy: study protocol for a randomized controlled trial

Abstract

Background: The 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/design: This 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.

Discussion: 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. The study result will help clinicians to choose between chlorthalidone and telmisartan in CCB-unresponsive patients.

Trial registration: ClinicalTrials.gov , NCT03226340. Registered on 2 December 2015.

Keywords: Angiotensin receptor blocker; Calcium channel blocker; Combination; Hypertension.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by each institutional review board: Hallym University Sacred Heart Hospital (approval number 2015-I110), Samsung Medical Center (approval number 2015-07-097), Korea University Guro Hospital (approval number KUGH 15145-001), KyungHee University Hospital (approval number KMC IRB 1527-05), Seoul National University Hospital (approval number, 1507-059-687), Asan Medical Center(approval number S2015-1140-0001), Hanyang University Hospital (approval number 2015-07-015), Ajou University School of Medicine (approval number MED-CT4-15-209), Kangdong Sacred Heart Hospital (approval number 2015-07-012), and Seoul National University Bundang Hospital (approval number B-1507/307-005), and is being carried out in compliance with the Declaration of Helsinki.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Overall scheme of the study

Fig. 2

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)