Efficacy of a digital therapeutics system in the management of essential hypertension: the HERB-DH1 pivotal trial

Abstract

Aims: Digital therapeutics is a new approach to facilitate the non-pharmacological treatment of hypertension using software programmes such as smartphone applications and/or device algorithms. Based on promising findings from a small pilot trial, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial investigated the efficacy of digital therapeutics in patients with hypertension not receiving antihypertensive medication.

Methods and results: This prospective, open-label, randomized controlled study was performed at 12 sites in Japan. Patients with hypertension [office systolic blood pressure (SBP) 140 to <180 mmHg and 24 h SBP ≥130 mmHg] were randomly assigned 1:1 to the digital therapeutics group (HERB system + standard lifestyle modification) or control group (standard lifestyle modification alone). The primary efficacy endpoint was the mean change in 24 h ambulatory SBP from baseline to 12 weeks; key secondary efficacy endpoints were mean changes in office and home blood pressure (BP) from baseline to 12 weeks. All analyses were conducted in the full analysis set population. Between December 2019 and June 2020, 390 patients were randomly assigned to the digital therapeutics group (n = 199) or control (n = 191) group. Between-group differences in 24-h ambulatory, home, and office SBPs at 12 weeks were -2.4 (95% confidence interval -4.5 to -0.3), -4.3 (-6.7 to -1.9), and -3.6 (-6.2 to -1.0) mmHg, respectively. No major programme-related safety events occurred up to 24 weeks.

Conclusion: The HERB-DH1 pivotal study showed the superiority of digital therapeutics compared with standard lifestyle modification alone to reduce 24-h ambulatory, home, and office BPs in the absence of antihypertensive medications.

Keywords: Ambulatory blood pressure; Digital therapeutics; Home blood pressure; Hypertension; Lifestyle modification.

Graphical abstract

Figure 1

Overview of the digital therapeutic intervention (HERB system) for essential hypertension.

Figure 2

CONSORT flow diagram. *Primary endpoint. ABPM, ambulatory blood pressure monitoring; BP, blood pressure.

Figure 3

Changes from baseline to 12 weeks in 24-h, daytime, and nighttime systolic blood pressure based on ambulatory blood pressure monitoring, morning and evening home systolic blood pressure, and office systolic blood pressure. Values are reported as mean [95% confidence interval]. ABPM, ambulatory blood pressure monitoring; SBP, systolic blood pressure.

Figure 4

Change in morning home systolic blood pressure from baseline to 24 weeks. Values are reported as mean and standard error (bars). P-values are for differences between groups in the change from baseline to each time point using analysis of covariance adjusted for study site, previous antihypertensive drug use, and baseline systolic blood pressure on ambulatory blood pressure monitoring. LM, guideline-based lifestyle modification; MED, prescribed antihypertensive medications at 12 weeks. *Statistically significant between-group difference in the change from baseline.

Figure 5

Differences in 24-h systolic blood pressure between the digital therapeutics and control groups at 12 weeks in patient subgroups. ABPM, ambulatory blood pressure monitoring; BMI, body mass index; CI, confidence interval; DBP, diastolic blood pressure; SBP, systolic blood pressure.