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Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.

In-Jeong Cho·Soon Jun Hong·Min Gyu Kong·Sang-Ho Jo·Eun Joo Cho·Cheol Ung Choi·Jung Hyun Choi·Dae-Hee Kim·Ju Han Kim·Sang-Hyun Ihm·Wook Bum Pyun
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Abstract

Many hypertensive patients require three or more antihypertensive agents to achieve target blood pressure. This randomized, double-blind, multicenter phase 3 trial conducted in South Korea evaluated the efficacy and safety of a single-pill triple combination therapy with valsartan (Val), amlodipine (Aml), and chlorthalidone (CTD) in patients whose blood pressure remained inadequately controlled on Val/Aml dual therapy. Patients uncontrolled after 4 weeks of Val/Aml 80/5&#xa0;mg were randomized 1:1 to either Val/Aml/CTD 80/5/12.5&#xa0;mg or Val/Aml 80/5&#xa0;mg using a double-dummy design. After 2 weeks, doses were escalated to Val/Aml/CTD 160/5/25&#xa0;mg or Val/Aml 160/5&#xa0;mg, respectively, for a total treatment duration of 6 weeks. The primary endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Of 193 randomized patients, 178 completed the study. The least squares mean &#xb1; SE change in MSSBP was -19.70 &#xb1; 1.31&#xa0;mmHg in the Val/Aml/CTD group versus -8.71 &#xb1; 1.26&#xa0;mmHg in the control group, yielding a statistically significant between-group difference of -10.99 &#xb1; 1.81&#xa0;mmHg (95% CI, -14.56 to -7.41; p < 0.0001). No serious adverse events occurred in the Val/Aml/CTD group, compared with an incidence of 1.98% in the control group (p = 0.4985). Triple combination therapy with Val/Aml/CTD demonstrated superior blood pressure reduction and a favorable safety profile in patients with essential hypertension inadequately controlled on Val/Aml dual therapy, supporting its use as an effective treatment option in this population. Trial Registration: This trial was prospectively registered at ClinicalTrials.gov (identifier: NCT06416865).

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HumansChlorthalidoneDouble-Blind MethodFemaleAmlodipineAntihypertensive AgentsMaleDrug Therapy, CombinationMiddle AgedTreatment OutcomeEssential HypertensionBlood PressureRepublic of KoreaValsartanAgedDrug CombinationsHypertensionamlodipinechlorthalidonehypertensionvalsartanJournal ArticleRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III

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In-Jeong Cho, Soon Jun Hong, Min Gyu Kong, Sang-Ho Jo, Eun Joo Cho, Cheol Ung Choi, Jung Hyun Choi, Dae-Hee Kim, Ju Han Kim, Sang-Hyun Ihm, Wook Bum Pyun. 2026. Efficacy and Safety of a Single-Pill Triple Combination of Valsartan, Amlodipine, and Chlorthalidone in Patients With Essential Hypertension Inadequately Controlled on Dual Therapy With Valsartan and Amlodipine: A Randomized, Double-Blind, Multicenter, Phase 3 Trial.. https://doi.org/10.1111/jch.70362

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Aged subjectBlood Pressure subjectClinical Trial, Phase III subjectDouble-Blind Method subjectDrug Combinations subjectDrug Therapy, Combination subjectFemale subjectHumans subjectHypertension subjectJournal Article subjectJournal Article; Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase III resourceMale subjectMiddle Aged subjectMulticenter Study subjectRandomized controlled trials study

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