Background: Medication safety in patients with polypharmacy at transitions of care is a focus of the current Third WHO Global Patient Safety Challenge. Medication review and communication between health care professionals are key targets to reduce medication-related harm.

Objective: To study whether a hospital discharge intervention combining medication review with enhanced information transfer between hospital and primary care physicians can delay hospital readmission and impact health care utilization or other health-related outcomes of older inpatients with polypharmacy.

Design: Cluster-randomized controlled trial in 21 Swiss hospitals between January 2019 and September 2020, with 6 months follow-up.

Participants: Sixty-eight senior physicians and their blinded junior physicians included 609 patients ≥ 60 years taking ≥ 5 drugs.

Interventions: Participating hospitals were randomized to either integrate a checklist-guided medication review and communication stimulus into their discharge processes, or follow usual discharge routines.

Main measures: Primary outcome was time-to-first-readmission to any hospital within 6 months, analyzed using a shared frailty model. Secondary outcomes covered readmission rates, emergency department visits, other medical consultations, mortality, drug numbers, proportions of patients with potentially inappropriate medication, and the patients' quality of life.

Key results: At admission, 609 patients (mean age 77.5 (SD 8.6) years, 49.4% female) took a mean of 9.6 (4.2) drugs per patient. Time-to-first-readmission did not differ significantly between study arms (adjusted hazard ratio 1.14 (intervention vs. control arm), 95% CI [0.75-1.71], p = 0.54), nor did the 30-day hospital readmission rates (6.7% [3.3-10.1%] vs. 7.0% [3.6-10.3%]). Overall, there were no clinically relevant differences between study arms at 1, 3, and 6 months after discharge.

Conclusions: The combination of a structured medication review with enhanced information transfer neither delayed hospital readmission nor improved other health-related outcomes of older inpatients with polypharmacy. Our results may help researchers in balancing practicality versus stringency of similar hospital discharge interventions.

Study registration: ISRCTN18427377, https://doi.org/10.1186/ISRCTN18427377.