The results of a Japanese Phase III domestic multicenter randomized controlled trial of a digital therapeutic app for hypertension (DTx) jointly developed by CureApp, Inc. (CEO Kohta Satake; hereafter “the Company”) and Jichi Medical University were presented by Professor Kazuomi Kario of Jichi University’s Department of Cardiovascular Medicine at the European Society of Cardiology Congress held at the end of August 2021 (ESC Congress 2021 – The Digital Experience: Late Breaking Trials in Hypertension). The results of this trial were also published in the European Heart Journal, one of the world’s leading journals on cardiovascular disease.
Summary of the clinical trial
This clinical trial*1 ran from January 2020 to December 2020 evaluating the efficacy and safety of the therapeutic app for patients with essential hypertension. This trial was performed as a comparative study of two groups, a control group who received guidance on lifestyle changes based on the Guidelines for the Management of Hypertension 2019 (hereafter, the “Guidelines”)*2, and an intervention group who used this therapeutic app in addition to applying lifestyle changes in accordance with said Guidelines.
This represented the world’s first trial of a therapeutic app for the purpose of regulatory approval in the field of hypertension.
Efficacy and clinical significance of the hypertension therapeutic app
The difference in the 24-hour systolic blood pressure between the groups (adjusted mean value) based on ABPM*3 at the study entry point of 12 weeks – the primary evaluation item – was -2.4 mmHg, indicating a significant hypotensive effect in the intervention group using the therapeutic app compared to the control group (Fig. 1).
The control group was provided guidance on lifestyle changes, and had their blood pressure monitored every day. A difference in the 24-hour systolic blood pressure between the groups based on ABPM of -2.4 mmHg represents a clinically significant change, reducing the risk of developing cardiovascular diseases and cerebrovascular diseases by 10.7%.*4
Further, the difference between the groups in terms of morning home SBP (systolic blood pressure) at the 12 week mark of the study was -4.3 mmHg (Fig. 1), an effect that was sustained until the 24 week mark. A J-HOP study*5 of patients at risk of cardiovascular disease in Japan found that morning home SBP is an independent risk factor for cerebral apoplexy, showing that an increase in systolic blood pressure of 10 mmHg increased the risk of a stroke by 36%. The 10 mmHg reduction of morning home SBP provided when using this therapeutic app demonstrates a clinically significant outcome in reducing cardiovascular diseases, while also demonstrating the effectiveness of the therapeutic app as an option for treating hypertension in the future.
ABPM: Ambulatory blood pressure monitoring,
Morning home SBP: Morning home systolic blood pressure
Evening home SBP: Evening home systolic blood pressure
Office SBP: Systolic blood pressure upon consultation
source: European Heart Journal, ehab559, https://doi.org/10.1093/eurheartj/ehab559
Hypertension is highly prevalent in Japan, with some 43 million*2 patients nationwide, and medical costs associated with hypertension upwards of around 1.8 trillion yen*6. Hypertension is the highest risk factor for cardiovascular and cerebrovascular diseases (stroke and heart disease), and an estimated 100,000 people*7 die of hypertension-induced cardiovascular and cerebrovascular diseases every year. Despite this, only 10 million people*8 are said to receive continuous treatment for hypertension, and mild stage medical intervention remains inadequate, with 70% of patients failing to meet their target blood pressure, or left untreated. While the importance of early adoption of sustainable lifestyle changes outside medical clinics and at home in order to maximize the benefit of treatments is being emphasized, there are large numbers of patients that are not receiving treatment at a medical clinic and, even for patients that are receiving treatment, there are limits to what doctors can achieve by providing individually-tailored lifestyle guidance within a limited consultation time frame.
The potential of a “therapeutic app” for hypertension
While lifestyle improvements are vital for treating hypertension, maintaining such changes is dependent on a patient’s values and motivation, their workplace and home environment, and other factors. This presents challenges for effective intervention by medical institutions.
In response to these issues, the DTx app automatically delivers personalized treatment guidance directly to the individual (optimal nutritional, exercise, and sleeping advice based on IoT blood pressure monitoring and lifestyle habit logs, and notifications prompting behavioral changes). This form of treatment encourages awareness and helps patients to adopt sustainable lifestyle changes, thereby providing a therapeutic effect that lowers blood pressure and alleviates hypertension. Doctors can also use the doctor’s app to check up on the lifestyle changes the patient has made, while the therapeutic app helps bring the patient and doctor closer together, improving the quality of medical care and facilitating the adoption of sustainable lifestyle changes.
*1 Kario K. Nomura A. Satake K. et al. A multicenter clinical trial to assess the efficacy of the digital therapeutics for essential hypertension: Rationale and design of the HERB-DH1 trial. J Clin Hypertens. (Greenwich) 2020;22(9):1713-1722 https://doi.org/10.1111/jch.13993
*2 Guidelines for the Management of Hypertension 2019 [JSH2019] The Japanese Society of Hypertension (2019) https://www.jpnsh.jp/guideline.html
*3 Ambulatory blood pressure monitoring (ABPM): Continuous blood pressure measurements taken at predetermined intervals over a 24 hour period during the course of one’s daily life. This helps determine variations in blood pressure (variation patterns over the course of a day). This is important due to the various factors which may alter one’s blood pressure.
*4 Is antihypertensive treatment based on home blood pressure recommended rather than that based on office blood pressure in adults with essential hypertension? Calculated based on the (meta-analysis) formula
Satoh M, Maeda T, Hoshide S, Ohkubo T. Is antihypertensive treatment based on home blood pressure recommended rather than that based on office blood pressure in adults with essential hypertension? (meta-analysis). Hypertens Res.2019;42:807-816.
*5 Hoshide S, Yano Y, Haimoto H, et al. Morning and Evening Home Blood Pressure and Risks of Incident Stroke and Coronary Artery Disease in the Japanese General Practice Population: The Japan Morning Surge-Home Blood Pressure Study. J-HOP Study Group.Hypertension. 2016;68:54-61.
*6 “Medical Care Expenditure Summary” 2018 Study (Ministry of Health, Labour and Welfare)
*7 “Vital Statistics Summary” 2019 Study (Ministry of Health, Labour and Welfare)
*8 “Patient Study” 2017 Study (Ministry of Health, Labour and Welfare)
Details on the presentation and paper releasing the results of this clinical trial
[European Society of Cardiology (ESC Congress 2021 – The Digital Experience)]
Late Breaking Trials in Hypertension
Speaker: Kazuomi Kario Jichi Medical University – Tochigi, Japan
[European Heart Journal]
Efficacy of a digital therapeutics system in the management of essential hypertension: the HERB-DH1 pivotal trial
European Heart Journal, ehab559, https://doi.org/10.1093/eurheartj/ehab559
First approved in Japan in 2020.