Efficacy and safety of low-dose antihypertensive combination of amlodipine, telmisartan, and chlorthalidone: A randomized, double-blind, parallel, phase II trial

Abstract

The aim of this clinical trial was to assess the efficacy and safety of low-dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a 2-week placebo run-in period, 176 patients were randomized to seven treatment groups (placebo, quarter-dose combination, third-dose combination, half-dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter-dose and half-dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP-lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third-dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third-dose group showed similar results with regard to the BP-lowering effect as the quarter-dose and half-dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low-dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP-lowering effect in patients with essential hypertension without any safety concerns.

Trial registration: ClinicalTrials.gov NCT04218552.

Keywords: amlodipine; chlorthalidone; hypertension; low-dose combination; telmisartan.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.

Figures

FIGURE 1

Flowchart of the study design

FIGURE 2

Subject disposition

FIGURE 3

Changes in systolic blood pressure (BP) from baseline to Week 4 (A) and Week 8 (B). Values are presented as the mean ± standard error. p = difference with the placebo group, p1 = difference with the amlodipine 5 mg group, p2 = difference with the amlodipine 10 mg group, p3 = difference with the telmisartan 80 mg. *Significant at the 5% level

FIGURE 4

Control rate of blood pressure at Week 4 and Week 8

FIGURE 5

BP response rate defined as a reduction of MSSBP by more than 20 mmHg and (A)/or (B) a reduction of MSDBP by more than 10 mmHg. BP, blood pressure; MSDBP, mean sitting diastolic BP; MSSBP, mean sitting systolic BP

FIGURE 6

Change of systolic blood pressure (BP) from baseline at Week 8 (additional analysis)