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

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

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Full details of study inclusion and exclusion criteria have been published previously.Briefly, eligible patients were aged 20 to 64 years, had a diagnosis of essential hypertension (office BP 140 to 179/90 to 109 mmHg) with mean 24 h BP determined using ambulatory BP monitoring of more 130 mmHg, did not use antihypertensive medication for more 3 months prior to enrolment, were able to use a smartphone daily, and were considered appropriate to be managed with lifestyle modification for 12 weeks. Patients with suspected secondary hypertension or who required immediate antihypertensive medication due to medical history or comorbidities were excluded.

Randomization (1:1) was performed automatically using the electronic data capture system. Randomization was stratified by the following factors: study centre, history of antihypertensive medication use (more 3 months previously), and 24-h SBP at baseline (more 145 or less 145 mmHg). Study visits took place at Weeks 4, 8, and 12 after randomization. In addition, patients were further evaluated after the end of study intervention (at Weeks 16, 20, and 24) and were divided into subgroups based on the antihypertensive medication usage within each randomized group.

A total of 91 patients (45.5%) in the digital therapeutics group and 54 (27.8%) in the control group reported any adverse event during the study ; none of these were considered to be related to the digital therapeutics system. There were two serious adverse events in each group: one admitted to hospital for pulmonary embolism in the digital therapeutics group and one lymphoma in the control group. No psychological adverse events were reported in either group.

Primary endpoint The mean change from baseline to 12 weeks in 24-h ambulatory SBP was significantly greater in the digital therapeutics vs. control group (-4.9 vs. -2.5 mmHg; between-group difference -2.4, 95% confidence interval (CI) -4.5 to -0.3, P = 0.024). Results were consistent in a sensitivity analysis using the per-protocol population (between-group difference -2.4 mmHg, 95% CI -4.5 to -0.3, P = 0.026). Secondary endpoints Compared with the control group, patients in the digital therapeutics group showed significantly greater reductions from baseline in morning home SBP (between-group difference -4.3 mmHg, 95% CI -6.7 to -1.9, P 0.001), evening home SBP (between-group difference -3.3 mmHg, 95% CI -5.8 to -0.7, P = 0.013), and office SBP (between-group difference -3.6 mmHg, 95% CI -6.2 to -1.0, P = 0.006) . Reductions from baseline in ambulatory, home and office DBP and heart rate were also significantly greater in the digital therapeutics group vs. control . The proportion of patients achieving morning home BP less 135/85 mmHg at 12-week follow-up was 22.2% in the digital therapeutics group and 10.4% in the control group.

The study was an open-label, randomized controlled trial in Japan. Patients with hypertension were randomly assigned 1:1 to the treatment group (HERB system plus standard lifestyle modification) or the control group (standard lifestyle modification only). he primary endpoint was the change from baseline in ABPM 24-hour SBP, and the treatment group showed a significant antihypertensive effect compared to the control group.

Aug. 27, 2021

Aug. 27, 2021

https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab559/6358480

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2032190148

Kario Kazuomi

Jichi Medical University Hospital

3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken, Japan 329-0498

kkario@jichi.ac.jp

Nakagawa Kiyose

CureApp, Inc.

Kodenma-Cho YS building 4th floor 12-5, Nihonbashi Kodenma-Cho, Chuo-ku, Tokyo

+81-3-6231-0183

clin-reg@cureapp.jp

Complete

Nov. 29, 2019

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

(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.

(1) SBP in clinical settings: >=180 mmHg; and/or DBP in clinical settings: >=110 mmHg
(2) Patients who were diagnosed as secondary hypertension
(3) Patients who have received (will receive) medications/combination therapy that are restricted to use by the study protocol
(4) Patients who should be treated with antihypertensive medications based on their disease record, comorbidities, and risk of cerebrocardiovascular disease
(5) Patients who are pregnant, suspected of being pregnant, or breastfeeding, or patients who are willing to get pregnant during the study period
(6) Patients who have received renal denervation for hypertension
(7) Patients who do not use a smartphone on a daily basis
(8) Patients who have participated in other clinical trials within 28 days. Or patients who have participated in a clinical study related to the smartphone application "HERB"
(9) Patients whose family members or partners living together are participating in this trial
(10) Patients who are judged to be inappropriate to participate in this study by the principal investigator or a subinvestigator due to other reasons

Both

essential hypertension

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.

hypertension

Life style modification

D000075222

D008019

Change in 24-hour SBP measured by ABPM from baseline to week 12

(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

Oct. 24, 2019

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