Home-Based, Remotely-Delivered Exercise Training to Improve Physical Function of Middle-aged and Older Sepsis Survivors – the HEAL Sepsis Trial (Preprint)

<sec> <title>BACKGROUND</title> Sepsis survivors frequently experience post-discharge physical function decline and encounter logistical barriers to participation in traditional outpatient rehabilitation. </sec> <sec> <title>OBJECTIVE</title> This pilot study examined the feasibility, safety, and preliminary efficacy of a remotely delivered, home-based exercise program on physical function in middle-age and older sepsis survivors. </sec> <sec> <title>METHODS</title> In this single-blinded, randomized controlled trial (RCT), we included sepsis survivors aged ≥55 years old and randomized them to 12 weeks of avatar-guided, progressive exercise training group (EX) or to a standard care control group (CO). Primary outcomes were feasibility (retention, adherence) and safety (adverse events), whereas secondary outcomes were changes in the 30-second Sit-to-Stand (30SSTS), 4-Stage Balance Test (4SBT), Timed Up-and-Go tests, and Eastern Cooperative Oncology Group/Zubrod's (ECOG/Zubrod) performance status score. Secondary outcomes were summarized as mean change, standard deviation, and effect sizes. </sec> <sec> <title>RESULTS</title> Twenty-one participants were randomized to either EX (n=10, mean age=69.6±8.5 years, 40% females) or CO (n=11, mean age=72.3±7.9 years, 45% females). Mean retention in the study was 95% and adherence to exercise training was 76%. Thirty-four adverse events (AEs) occurred (EX=12; CO=22 events), including four serious AEs that were unrelated to the study. The EX group demonstrated positive direction of change in lower-extremity strength (30SSTS: 1.14±2.91 repetitions, Cohen’s d=0.393) and balance (4SBT: 5.07±4.75 seconds, d=1.07). In contrast, the CO group showed minimal change in balance on the 4SBT (0.01±4.38 seconds, d=0.003) and a negative direction of change in lower-extremity strength on the 30SSTS (−0.88±0.99 repetitions, d=−0.883). Timed Up-and-Go performance showed modest reductions in completion time in both groups (EX: −1.42±6.58 seconds, d=−0.216; CO: −1.27±2.73 seconds, d=−0.466). ECOG/Zubrod scores also showed a positive direction of change in the EX group. </sec> <sec> <title>CONCLUSIONS</title> This pilot RCT demonstrated that a 12-week, remotely delivered exercise program was safe and feasible for middle-aged and older sepsis survivors. Preliminary signals of positive change in lower-extremity strength, balance, and functional status were observed, supporting the need for evaluation in a fully powered Phase IIb RCT targeting individuals at risk for post-discharge physical function decline. </sec> <sec> <title>CLINICALTRIAL</title> ClinicalTrials.gov NCT05568511. </sec>