Background: Weekly pharmacist-filled pill boxes improve medication organization, yet effects on blood pressure (BP) are inconsistent and short-lived when adherence is measured indirectly. Connected pill organizers that log dose-time events and deliver automated reminders enable objective adherence feedback and may enhance BP control at scale.
Objective: To determine whether a connected smart pill-box service reduces 24-h ambulatory blood pressure monitoring (ABPM) systolic BP (SBP) at 6 months compared with a pharmacist-filled weekly pill-box service among adults with uncontrolled hypertension.
Design: Multisite, parallel-group randomized controlled trial (1:1) with 6-month primary endpoint and 12-month maintenance follow-up.
Participants: Adults with uncontrolled hypertension on  ≥ 2 antihypertensives from primary care or veteran clinics; inclusive of caregiver-supported medication management and diverse literacy levels.
Interventions: Smart arm: connected organizer with dose-time logging, app/SMS nudges, and monthly pharmacist feedback based on device data. Control arm: pharmacist-filled weekly pill boxes (enhanced usual care). Protocolized medication titration allowed in both arms.
Primary Outcome: Change in 24-h ambulatory blood pressure monitoring (ABPM) SBP from baseline to 6 months.
Key Secondary Outcomes: Time-in-target SBP, automated office BP, electronic adherence (% on-time doses), medication changes, serious adverse events (syncope, AKI, hyperkalemia), ED/inpatient utilization, usability/acceptability, and cost per controlled patient.
Sample Size: Detecting a between-group difference of 4mmHg (SD 12mmHg), two-sided α = 0.05, 80–90% power requires 142–189 per arm; inflated by 15% for attrition.
Conclusions: SMART-BOX tests an objective-adherence, scalable strategy with 24-h ambulatory blood pressure monitoring (ABPM) endpoints and concurrent economic evaluation to inform routine hypertension care.