Low-Dose TEL/AML/CHTD SPC Versus Standard-Dose TEL in Hypertension: Phase III RCT

BACKGROUND: Although low-dose triple single-pill combination therapies show promising efficacy and safety, studies comparing them to standard-dose monotherapies remain limited. This phase III, randomized, double-blind trial evaluated the efficacy and safety of a low-dose single-pill combination of telmisartan, amlodipine, and chlorthalidone versus standard-dose telmisartan monotherapy in patients with essential hypertension. METHODS: After a 4-week placebo run-in period, 314 eligible subjects were randomized to either receive telmisartan/amlodipine/chlorthalidone 20/2.5/6.25 mg or telmisartan 40 mg for 8 weeks. The primary efficacy end point was the change in mean sitting systolic blood pressure from baseline to week 8, with noninferiority assessed in the per-protocol set (PPS), followed by superiority testing in the full analysis set using a gatekeeping approach to control for type I error. RESULTS: At week 8, the combination group demonstrated significant mean sitting systolic blood pressure reduction compared with monotherapy in the per-protocol set analysis (least squares mean difference, −3.8 mm Hg [95% CI: −6.7 to −0.9]; P =0.01), establishing its noninferiority. Furthermore, the superiority of the combination therapy was confirmed in the full analysis set (LS mean difference, −4.0 mm Hg [95% CI, −6.8 to −1.3]; P