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Randomized Controlled Trial
, 19 (7), e246

Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients With Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-Randomized Pilot Clinical Trial

Affiliations
Randomized Controlled Trial

Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients With Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-Randomized Pilot Clinical Trial

Juan Frias et al. J Med Internet Res.

Abstract

Background: Hypertension and type 2 diabetes mellitus are major modifiable risk factors for cardiac, cerebrovascular, and kidney diseases. Reasons for poor disease control include nonadherence, lack of patient engagement, and therapeutic inertia.

Objective: The aim of this study was to assess the impact on clinic-measured blood pressure (BP) and glycated hemoglobin (HbA1c) using a digital medicine offering (DMO) that measures medication ingestion adherence, physical activity, and rest using digital medicines (medication taken with ingestible sensor), wearable sensor patches, and a mobile device app.

Methods: Participants with elevated systolic BP (SBP ≥140 mm Hg) and HbA1c (≥7%) failing antihypertensive (≥2 medications) and oral diabetes therapy were enrolled in this three-arm, 12-week, cluster-randomized study. Participants used DMO (includes digital medicines, the wearable sensor patch, and the mobile device app) for 4 or 12 weeks or received usual care based on site randomization. Providers in the DMO arms could review the DMO data via a Web portal. In all three arms, providers were instructed to make medical decisions (medication titration, adherence counseling, education, and lifestyle coaching) on all available clinical information at each visit. Primary outcome was change in SBP at week 4. Other outcomes included change in SBP and HbA1c at week 12, and low-density lipoprotein cholesterol (LDL-C) and diastolic blood pressure (DBP) at weeks 4 and 12, as well as proportion of patients at BP goal (<140/90 mm Hg) at weeks 4 and 12, medical decisions, and medication adherence patterns.

Results: Final analysis included 109 participants (12 sites; age: mean 58.7, SD years; female: 49.5%, 54/109; Hispanic: 45.9%, 50/109; income ≤ US $20,000: 56.9%, 62/109; and ≤ high school education: 52.3%, 57/109). The DMO groups had 80 participants (7 sites) and usual care had 29 participants (5 sites). At week 4, DMO resulted in a statistically greater SBP reduction than usual care (mean -21.8, SE 1.5 mm Hg vs mean -12.7, SE 2.8 mmHg; mean difference -9.1, 95% CI -14.0 to -3.3 mm Hg) and maintained a greater reduction at week 12. The DMO groups had greater reductions in HbA1c, DBP, and LDL-C, and a greater proportion of participants at BP goal at weeks 4 and 12 compared with usual care. The DMO groups also received more therapeutic interventions than usual care. Medication adherence was ≥80% while using the DMO. The most common adverse event was a self-limited rash at the wearable sensor site (12%, 10/82).

Conclusions: For patients failing hypertension and diabetes oral therapy, this DMO, which provides dose-by-dose feedback on medication ingestion adherence, can help lower BP, HbA1c, and LDL-C, and promote patient engagement and provider decision making.

Trial registration: Clinicaltrials.gov NCT02827630; https://clinicaltrials.gov/show/NCT02827630 (Archived by WebCite at http://www.webcitation.org/6rL8dW2VF).

Keywords: digital medicine; hypertension; patient engagement, medication adherence; therapeutic inertia; type 2 diabetes.

Conflict of interest statement

Conflicts of Interest: The sponsor, Proteus Digital Health, had a role in the design and conduct of the study; analysis and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication. The sponsor had no role in the collection or management of the study. JF reports consulting relationship with Proteus Digital Health, Johnson & Johnson, AstraZeneca, CeQur, and Sanofi. He also reports receiving study grants from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, Novo Nordisk, Pfizer, and Sanofi. NV, PR, YK, and GS are employed by Proteus Digital Health. GS is also a cofounder, officer, and stock owner of Proteus Digital Health. LO reports a consulting relationship with Proteus Digital Health; his contribution to this publication was as a paid consultant and was not part of his Stanford University duties or responsibilities.

Figures

Figure 1
Figure 1
Top left: ingestible sensor and ingestible sensor pill. Top right: coencapsulation of a medication with an ingestible sensor pill. Bottom: components of the DMO and data flow.
Figure 2
Figure 2
CONSORT flow diagram of participants.
Figure 3
Figure 3
Highlighted clinical results for changes in systolic and diastolic blood pressure (SBP and DPB), glycated hemoglobin (HbA1c), and low-density lipoprotein cholesterol (LDL-C) for the combined digital medicine offering (DMO) groups at week 4, week-4 DMO, and 12-week DMO. Error bars represent SE.
Figure 4
Figure 4
Ingestion adherence for DMO subjects measured by DMO. Note adherence for the first 4 weeks includes both 4-week DMO and 12-week DMO; adherence for 12 weeks includes only 12-week DMO.

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