Wearable-Based Physiologic Metrics Demonstrate Clinical Utility and Construct Validity in a Phase 3 Sickle Cell Disease Trial

ABSTRACT Adults with sickle cell disease (SCD) experience reduced physical capacity due to anemia and cardiopulmonary complications, yet objective real-world monitoring of disease burden remains limited. Wearable devices offer a scalable approach for remote assessment of activity and physiologic parameters, but feasibility in high-risk ambulatory SCD populations has not been established. We conducted baseline analyses of the wearable data in the SCD-CARRE trial, a multisite randomized controlled trial enrolling high-risk adults with SCD defined by elevated tricuspid regurgitant velocity (TRV ≥2.5 m/s), elevated NT-proBNP, or chronic kidney disease. Participants wore Garmin devices continuously for 7-day periods at baseline. Valid data were defined as ≥3 days with ≥10 hours of wear per day; feasibility was operationalized as >80% valid data collection among participants with available data. Of 173 randomized participants, 155 (89.6%) had baseline device data available. Among those, 132 (85.2%) met the wear time requirement. Median daily wear time was 22.3 hours (IQR 21.1, 23.1), indicating near-continuous monitoring. Median daily step count was3,700 (IQR 2,200, 5,800), varying by country (Brazil 5,600, France 4,300, US 3,400), with sedentary time of 20.3 hours/day and mean heart rate of 80.1 bpm. Wearable-derived activity metrics declined progressively with worsening WHO functional class and increased with greater six-minute walk distance. TRV was negatively associated with daily steps and active time, and NT-proBNP with average heart rate, but wide between-person variability reduced confidence in interpreting these cross-sectional associations. This is the largest study to demonstrate feasible remote wearable monitoring in a geographically diverse, multinational cohort of adults with SCD, supporting wearable devices as objective patient-centered endpoints for interventional trials. This trial was registered at www.clinicaltrials.gov as #NCT04084080.