Efficacy and Safety of a Novel Low-Dose Triple Single-Pill Combination ComparedWith Placebo for Initial Treatment of Hypertension.

Abstract

Single-pill combinations of 3 or more low-dose blood pressure (BP)-lowering drugs hold promise for initial or early treatment of hypertension. We conducted a placebo-controlled trial of a new single-pill combination containing low doses of telmisartan, amlodipine, and indapamide in 2 dose options to assess efficacy and safety. This international, randomized, double-blind, placebo-controlled, parallel-group trial enrolled adults with hypertension receiving 0 to 1 BP-lowering drugs. After a 2-week placebo run-in during which any BP-lowering medication was stopped, participants were eligible if home systolic BP (SBP) was 130 to 154mmHg. Participants were randomized in a 2:2:1 ratio to GMRx2 ¼ dose (telmisartan 10mg/amlodipine 1.25mg/indapamide 0.625mg), GMRx2 ½ dose (telmisartan 20mg/amlodipine 2.5mg/indapamide 1.25mg), or placebo. The primary efficacy outcome was difference in change in home SBP from randomization to week 4, and primary safety outcome was treatment discontinuation due to an adverse event. From June 14, 2021 to October 18, 2023, a total of 295 participants (mean age: 51 years; 56% female) were randomized and 96% completed the trial. Baseline mean home BP was 139/86mmHg and clinic BP was 138/86mmHg after placebo run-in. The placebo-corrected least square mean differences in home SBP at Week 4 were-7.3mmHg (95% CI: -4.5 to-10.2) for GMRx2 ¼ dose and-8.2mmHg (95% CI: -5.2 to-11.3) for GMRx2 ½ dose; reductions for clinic BP were 8.0/4.0 and 9.5/4.9mmHg. At Week 4, clinic BP control (<140/90mmHg) was 37%, 65%, and 70% for placebo, GMRx2 ¼ dose, and GMRx2 ½ dose, respectively (both doses P< 0.001 vs placebo). Placebo, GMRx2-triple ¼, and GMRx2 ½ treatment discontinuation due to an adverse event occurred in 1 (1.6%), 0, and 6 (5.1%), respectively; out of normal range serum sodium or potassium was observed in 4 (6.3%), 12 (10.6%), and 12 (10.1%), respectively, but no participant had a serum sodium<130/>150mmol/L or potassium<3.0/>6.0mmol/L. Serious adverse events were reported by 2 participants in the placebo and GMRx2 ½ groups and none in the GMRx2 ¼ group. In a population with mild-to-moderate BP elevation, both dose versions of the novel low-dose triple single-pill combination showed good tolerability and clinically relevant BP reductions compared with placebo. (Efficacy and Safety of GRMx2 Compared to Placebo for the Treatment of Hypertension: NCT04518306).