Efficacy and safety of a smartphone application "HERB" added to treatment as usual for essential hypertension: a multicenter randomized controlled phase III study

INTERVENTION: HERB is a digital therapeutic system to be adapted to the standard treatment for hypertension. The system consists of HERB Mobile: a smartphone app for patients, HERB Console: a web application for doctors and healthcare workers. HERB Mobile aims to improve hypertension through lifestyle modification. It encourages optimal behavioral change for each patient. Doctors and healthcare workers can also check the status of lifestyle modification situations through HERB Console. HERB Console supports doctors and healthcare professionals providing better treatment instruction for patients. CONDITION: D000075222 essential hypertension ; hypertension PRIMARY OUTCOME: Change in 24‐hour SBP measured by ABPM from baseline to week 12 INCLUSION CRITERIA: (1) 20 years old or older and under 65 years old (2) Systolic blood pressure (SBP) in clinical settings: >=140 mmHg; <=179 mmHg, and/or diastolic blood pressure (DBP) in clinical settings: >=90=< and <=109 mmHg (3) 24‐hour averaged SBP of ambulatory blood pressure monitoring (ABPM) at the screening phase: >=130 mmHg (4) Patients who have not received antihypertensive medication (including those who have not received antihypertensive treatment for more than 3 months at the time of obtaining consent) (5) Patients who use a smartphone (with iOS or Android) on a daily basis (6) Patients who agree to perform ABPM at the screening phase, 12 weeks, and 24 weeks after enrollment (7) Patients with hypertension who were judged to be appropriate for the lifestyle modification treatment without antihypertensive medication by the principal investigator or a subinvestigator. SECONDARY OUTCOME: (1); ‐ Amount of change in 24‐hour averaged SBP measured by ABPM from baseline to week 12; (2); ‐ Amount of change in 24‐hour averaged SBP measured by ABPM from baseline to week 24; ‐ The proportion of participants who satisfy the following targets at week 12 and week 24; ‐ target 1: home SBP < 135 mmHg and home DBP < 85 mmHg; ‐ target 2: home SBP < 125 mmHg and home DBP < 75 mmHg; ‐ The proportion of participants whose 24‐hour averaged SBP by ABPM at week 24 is lowered by more than 5 mmHg compared to week 12 ; ‐ Change in 24‐hour averaged DBP measured by ABPM from baseline to week 12 and week 24; ‐ Change in daytime and nighttime averaged SBP and DBP measured by ABPM from baseline to week 12 and week 24; ‐ Change in pulse pressure (24‐hour, daytime, and nighttime) measured by ABPM from baseline to week 12 and week 24; ‐ Change in pulse (24‐hour, daytime, and nighttime) measured by ABPM from baseline to week 12 and week 24; ‐ Change in 24‐hour averaged SBP and DBP measured by ABPM from baseline to week 12 and week 24 among the Non‐dipper subgroup (defined as participants with a drop of less than 10% in nighttime blood pressure during the circadian rhythm) ; ‐ Ambulatory SBP and DBP variability (defined as a value obtained by dividing the standard deviation of blood pressure by the average value, for 24‐hour, daytime, and nighttime); ‐ Change in 7‐day averaged (or at least 5 days excluding office visit) home SBP and DBP right after waking up and right before going to bed from baseline to week 12 and week 24; ‐ Change in 7‐day averaged (or at least 5 days excluding office visit) home pulse right after waking up and right before going to bed from baseline to week 12 and week 24; ‐ Change in 7‐day averaged (or at least 5 days excluding office visit) home SBP and DBP variability right after waking up and right before going to bed from baseline to week 12 and week 24; ‐ Change in clinic SBP and DBP from baseline to week 12 and week 24; ‐ Change in clinic pulse from baseline to week 12 and week 24; ‐ Change in body weight, Body Mass Index, and waist circumference from baseline to week 12 and week 24; ‐ Change in the score of the salt check sheet from baseline to week 12 and week 24; ‐ Blood test results (complete blood cell count, blood urea nitrogen, creatinine, uric acid, sodium, potassium, chlorine, total cholesterol, total glycerides, HDL‐cholesterol, LDL‐cholesterol, fasting plasma glucose, HbA1c, alanine aminotransferase, aspartate transaminase, gamma‐glutamyltransferase, eGFR) at week 12 and at week 24; ‐ urine sodium (mEq/gCr), urine potassium (mEq/gCr) at week 12 and at week 24; ‐ HERB Mobile utilization rate, program progress, the progress of habituation, rate of blood pressure measurement, rate of self‐monitoring until week 12 and until week 24; ‐ the number of adverse events, the number of software malfunction until week 12 and until week 24; ; (3); ‐ the proportion of patients who used concomitant antihypertensive drugs, types of concomitant antihypertensive drugs, and their dose; ‐ Change in SBP and DBP (24‐hour, daytime, and nighttime, averaged) measured by ABPM from week 12 to week 24; ‐ Change in 7‐day averaged (or at least 5 days excluding office visit) home SBP and DBP right after waking up and right before going to bed from week 12 to week 24