Rationale and design of a multicenter randomized study comparing the efficacy and safety of esaxerenone versus trichlormethiazide in patients with uncontrolled essential hypertension: EXCITE-HT study

J Clin Hypertens (Greenwich). 2023 Sep;25(9):861-867. doi: 10.1111/jch.14705. Epub 2023 Aug 7.

Abstract

The next-generation mineralocorticoid receptor blocker (MRB) esaxerenone has favorable antihypertensive effects in patients who do not respond to treatment with first-line antihypertensive agents and may be beneficial as a second-line treatment. However, MRBs are currently considered a fourth-line treatment as there is no clinical evidence comparing the efficacy of esaxerenone with other classes of antihypertensive agents. The multicenter, randomized, open-label, parallel-group EXCITE-HT study will evaluate the efficacy and safety of esaxerenone as a second-line agent in the treatment of Japanese patients with uncontrolled essential hypertension. After a 4-week run-in period, patients will receive either esaxerenone or trichlormethiazide for 12 weeks per the package insert and the Japanese Society of Hypertension Guidelines for the Management of Hypertension. At Weeks 4 and 8, the dose of esaxerenone or trichlormethiazide may be increased. Blood pressure (home [morning and bedtime] and office), serum biomarkers, and urinary biomarkers will be measured. The primary efficacy endpoint is the change from baseline in morning home systolic blood pressure/diastolic blood pressure to the end of treatment. The EXCITE-HT study is expected to validate the non-inferiority of esaxerenone to trichlormethiazide and provide the first evidence for the early use of esaxerenone as a second-line agent in the treatment of Japanese patients with uncontrolled essential hypertension instead of its current use as a fourth-line agent.

Keywords: esaxerenone; hypertension; mineralocorticoid receptor blockers; randomized comparative study; trichlormethiazide.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents* / adverse effects
  • Blood Pressure
  • Essential Hypertension / drug therapy
  • Humans
  • Hypertension*
  • Trichlormethiazide / pharmacology
  • Trichlormethiazide / therapeutic use

Substances

  • Antihypertensive Agents
  • Trichlormethiazide
  • esaxerenone