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Triple-Combination Therapy with Olmesartan, Amlodipine, and Hydrochlorothiazide in Black and Non-Black Study Participants with Hypertension

The TRINITY Randomized, Double-Blind, 12-Week, Parallel-Group Study

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Abstract

Background

Although awareness of hypertension in Black patients has increased, blood pressure (BP) is frequently inadequately controlled.

Objective

This prespecified subgroup analysis of the TRINITY study evaluated the efficacy and safety of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the component dual-combination treatments in Black and non-Black study participants.

Study Design

TRINITY was a 12-week, randomized, double-blind, parallel-group evaluation. The first patient was enrolled in May 2008 and the last patient completed the study in February 2009. The study consisted of a 3-week washout period for participants receiving antihypertensive therapy and a 12-week double-blind treatment period. For the treatment phase, all study participants were stratified by age, race, and diabetes mellitus status and randomized to a treatment sequence that led to their final treatment assignment, which they received from weeks 4 to 12 (OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg). In the first 2 weeks of the double-blind treatment period, all participants received either dual-combination treatment or placebo. Participants assigned to dual-combination treatment continued treatment until week 4, and participants receiving placebo were switched at week 2 to receive one of the dual-combination treatments until week 4. At week 4, participants either continued dual-combination treatment or randomly received triple-combination treatment until week 12.

Setting

317 clinical sites in the USA and Puerto Rico were included in the study.

Patients

Study participants eligible for randomization (N = 2492) were ≥18 years of age with mean seated blood pressure (SeBP) ≥140/100 mmHg or ≥160/90 mmHg (off antihypertensive medication).

Intervention

The intervention was with dual- or triple-combination antihypertensive treatment: OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg.

Main Outcome Measure

The primary efficacy variable was the change in least squares (LS) mean seated diastolic BP (SeDBP) from baseline to week 12. Secondary efficacy variables included the LS mean change in seated systolic BP (SeSBP), percentage of study participants reaching BP goal, and safety parameters.

>Results

In both Black and non-Black participants, triple-combination treatment resulted in significant and similar mean reductions in SeDBP and SeSBP (p≤0.0001 vs each dual-combination treatment) with a greater proportion of participants reaching BP goal compared with dual-combination treatments, regardless of race. Most treatment-emergent adverse events were mild or moderate in severity and no new safety concerns were identified.

Conclusion

Triple-combination treatment provided greater BP reductions than dual-combination treatments regardless of race.

Clinical Trial Registration

Registered at ClinicalTrials.gov as NCT00649389.

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Acknowledgments and Disclosures

Research funds for this study were provided by Daiichi Sankyo, Inc., Parsippany, NJ, USA. The trial was designed by Daiichi Sankyo, Inc. in conjunction with the investigators. All authors contributed to the study design; data analysis/interpretation; drafting, critical revision, and approval of the manuscript. Medpace, Inc. (Cincinnati, OH, USA), a contract research organization, performed project management, data management, clinical and safety monitoring, and statistical analysis in conjunction with Daiichi Sankyo, Inc. Editorial support for this article was provided by Vrinda Mahajan, PharmD, of Peloton Advantage, LLC, Parsippany, NJ, funded by Daiichi Sankyo, Inc. The opinions expressed in the current article are those of the authors. The authors received no honoraria/fees for service or other form of financial support related to the development of this article.

Steven G. Chrysant, MD, has served as a consultant and speakers bureau member for and received grant/research support and honoraria from Daiichi Sankyo, Inc. Joseph L. Izzo, MD, Jr, has served as a consultant or investigator for Daiichi Sankyo, Inc., Boehringer-Ingelheim, Novartis Pharmaceuticals, GlaxoSmithKline, Takeda Pharmaceuticals, and Forest Laboratories. Dean J. Kereiakes, MD, reports no disclosure information. Suzanne Oparil, MD, has received grant/research support from Merck & Co., Medtronic, Novartis, and Takeda, and has served as a consultant for Bayer, Daiichi Sankyo, Inc, Medtronic, Novartis, and Pfizer Inc. Michael Melino, PhD, James Lee, PhD, and Victor Fernandez, BS, are employees of Daiichi Sankyo, Inc. Reinilde Heyrman, MD, is a former employee of Daiichi Sankyo, Inc.

Author information

Authors and Affiliations

  1. Oklahoma Cardiovascular and Hypertension Center, University of Oklahoma College of Medicine, 5850 Wilshire Blvd, Oklahoma City, Oklahoma, OK 7313, USA

    Steven G. Chrysant MD, PhD

  2. Piedmont Medical Research Associates, Winston-Salem, North Carolina, USA

    Thomas Littlejohn III

  3. State University of New York at Buffalo, Buffalo, New York, USA

    Joseph L. Izzo Jr

  4. The Christ Hospital Heart and Vascular Center, The Carl and Edyth Lindner Center for Research and Education at the Christ Hospital, Cincinnati, Ohio, USA

    Dean J. Kereiakes

  5. University of Alabama at Birmingham, Birmingham, Alabama, USA

    Suzanne Oparil

  6. Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

    Michael Melino, James Lee & Victor Fernandez

  7. Formerly of Daiichi Sankyo, Inc., Parsippany, New Jersey, USA

    Reinilde Heyrman

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  1. Steven G. Chrysant MD, PhD
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Corresponding author

Correspondence to Steven G. Chrysant MD, PhD.

Additional information

The authors are saddened to report the passing in March 2011 of Thomas Littlejohn, III, MD, esteemed physician, investigator, colleague, and co-author of posters and publications from the TRINITY study. His contributions to this manuscript were invaluable.

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Chrysant, S.G., Littlejohn, T., Izzo, J.L. et al. Triple-Combination Therapy with Olmesartan, Amlodipine, and Hydrochlorothiazide in Black and Non-Black Study Participants with Hypertension. Am J Cardiovasc Drugs 12, 233–243 (2012). https://doi.org/10.1007/BF03261832

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