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. 2025 Oct;4(10 Pt 2):102175.
doi: 10.1016/j.jacadv.2025.102175. Epub 2025 Aug 29.

Efficacy and Safety of a Novel Triple Single-Pill for Uncontrolled Hypertension: The OPTION TREAT Trial

Vagner Madrini Jr  1 , Caio A M Tavares  2 , Monica T A Albuquerque  1 , Odilson M Silvestre  3 , João S Felicio  4 , Fabio S Silveira  5 , Miguel N Hissa  6 , Murillo O Antunes  7 , Marco A Mota-Gomes  8 , Maria H Vidotti  9 , Flávio D Fuchs  10 , Fabiana G Marcondes-Braga  11 , Conrado R H Filho  12 , Charlene Troiani do Nascimento  13 , Rafael A Bastos  14 , Andrea A Brandão  15 , Elizabeth E S Cestário  16 , Luiz A Bortolotto  17 , Vivienne C Castilho  18 , Maura G Lapa  18 , Erida A P Magaton  18 , Paula B Fernandes  18 , Camila S N Albuquerque  1 , Lucas R Silva  1 , Otávio Berwanger  19 , Patricia O Guimarães  20
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Free article

Efficacy and Safety of a Novel Triple Single-Pill for Uncontrolled Hypertension: The OPTION TREAT Trial

Vagner Madrini Jr et al. JACC Adv. 2025 Oct.
Free article

Abstract

Background: Novel single-pill combinations with blood pressure (BP)-lowering agents are needed to increase treatment options for hypertension.

Objectives: The purpose of this study was to assess the efficacy and safety of a novel single pill (candesartan cilexetil, amlodipine, and chlorthalidone) compared with an active control (valsartan, amlodipine, and hydrochlorothiazide) for uncontrolled hypertension.

Methods: OPTION TREAT (Efficacy and Safety of a Novel Triple Single-Pill Combination Therapy Compared with an Active Control in Patients with Uncontrolled Hypertension) was a randomized, double-blind, double-dummy, noninferiority trial conducted across 19 sites in Brazil. Participants with an office systolic BP of 140 to 180 mm Hg and a diastolic BP of 90 to 110 mm Hg despite dual therapy were randomized in a 1:1 ratio to receive either the experimental treatment or the active control for 12 weeks. The primary outcome was the mean change in office systolic BP from baseline to week 12. The prespecified noninferiority margin was 3 mm Hg. Secondary outcomes included mean changes in diastolic BP and adverse events.

Results: Overall, 703 participants were included (mean age 57.8 years, 62.7% women, baseline office BP of 153.0/95.6 mm Hg). At 12 weeks, the least square mean change in systolic BP was -22.6 mm Hg in the experimental group vs -18.2 mm Hg in the control group (between-group difference -4.4 mm Hg; 90% CI -6.3 to -2.5 mm Hg; P < 0.001). Diastolic BP was also reduced in both groups, with greater reductions in the experimental group (-13.8 mm Hg vs -12.0 mm Hg; P = 0.008). Adherence was high, and serious adverse events were rare.

Conclusions: In patients with uncontrolled hypertension, a novel triple single-pill containing candesartan cilexetil, amlodipine, and chlorthalidone improved BP control at 12 weeks and had a reasonable safety profile. (Candesartan Cilexetil + Chlorthalidone + Amlodipine Versus Exforge HCT for Systemic Arterial Hypertension [OPTION TREAT]; NCT05920005).

Keywords: blood pressure control; fixed-dose combination; hypertension; single-pill combination; triple therapy.

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Conflict of interest statement

Funding support and author disclosures This study was funded by Libbs Pharmaceuticals. Dr Madrini Jr has received lecture fees from Bristol Myers Squibb, Novartis, and Bayer outside the submitted work. Dr Tavares has received lecture fees from Novo Nordisk outside the submitted work. Dr Berwanger has received research grants from Bayer paid to his current institution and research grants from AstraZeneca, Bayer, Servier, Amgen, Pfizer, and Novartis paid to his former institution. Drs Castilho, Lapa, Magaton, and Fernandes are employees of Libbs Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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