Low-Dose Telmisartan/Amlodipine in Essential Hypertension: A Phase III Trial

Abstract

Low-dose single-pill combinations (SPCs) are gaining recognition as an efficient therapeutic strategy for mild hypertension. However, evidence from randomized controlled trials regarding the efficacy and safety of half-dose telmisartan/amlodipine SPCs remains limited. In this randomized, double-blind, active-controlled phase III trial, patients with essential hypertension [mean sitting systolic blood pressure (MSSBP) ≥ 140 and < 180 mmHg] were allocated to four treatment arms to receive either telmisartan/amlodipine 20/2.5 mg SPC (TEL/AML 20/2.5), or monotherapy with telmisartan 20 mg (TEL 20), amlodipine 2.5 mg (AML 2.5), or telmisartan 40 mg (TEL 40) once daily for 8 weeks. The primary endpoint was the change in MSSBP from baseline to week 8. A gatekeeping approach was used to test the superiority of TEL/AML 20/2.5 over TEL 20 and AML 2.5, followed by non-inferiority versus TEL 40. At week 8, TEL/AML 20/2.5 showed significantly greater MSSBP reductions compared with TEL 20 [least squares mean (LSM) differences: −5.79 mmHg; p = 0.0003] and AML 2.5 (−8.57 mmHg; p < 0.0001). Non-inferiority to TEL 40 was established, with an LSM difference of −3.88 mmHg (95% Confidence Interval: −6.67 to −1.09), which met the pre-specified 3 mmHg margin. The overall incidence of adverse events was 8.05%, with no statistically significant differences between groups. Overall, TEL/AML 20/2.5 SPC provided superior BP-lowering efficacy compared with TEL 20 and AML 2.5 monotherapies and was non-inferior to TEL 40. With a comparable safety profile across treatment groups, these findings suggest that TEL/AML 20/2.5 is a practical and effective option for hypertension management. Trial Registration: ClinicalTrials.gov, NCT06052748.