Patient-centered deprescribing of opioid analgesics in hospitalized adults from admission to post-discharge: the iPROACTIVE study protocol of a pragmatic randomized controlled trial

Abstract Background Opioid overprescription has prompted a re-evaluation of pain management practices. Although opioid therapy is often initiated in hospitals, there is a lack of standardized discharge protocols for dose reduction, which leaves patients vulnerable to continued use of opioid analgesics. The iPROACTIVE randomized controlled trial evaluates an interprofessional opioid exit plan combining physician-pharmacist counseling with individualized dosing recommendations to reduce time to baseline opioid use while maintaining pain control and patient safety. Methods This investigator-initiated, monocentric, open, randomized controlled trial is conducted at a Swiss medical teaching hospital. The study population includes hospitalized adults (18 years or over) who have received continuous opioid therapy for at least three consecutive days with a clinically indicated dose reduction confirmed by the case-leading physician. Key exclusion criteria are limited cognitive capacity to participate in educational interventions, treatment in critical care settings, pregnancy, cancer-related pain management, and end-of-life care. The intervention comprises a newly developed deprescribing strategy delivered by an interprofessional team of hospital pharmacists and physicians specialized in internal medicine or pain medicine. The intervention is delivered during hospitalization, at discharge, and during 3-month follow-up, and includes individualized opioid reduction recommendations, educational materials, and provision of blister packages. Control group patients receive usual care at the discretion of the case-leading physician. The primary endpoint measure is the time to return to prehospitalization morphine milligram equivalent doses, analyzed using log-rank tests and Kaplan-Meier survival curves. The study employs a two-armed design with blocked randomization stratified by medical department (internal medicine versus surgery) and prior opioid use (preexisting versus new). Study procedures are embedded within routine clinical workflows, allowing integration into existing ward rounds, medication reconciliation processes, and discharge planning. The planned sample size is 86 participants, with equal allocation of 43 participants per study arm. Discussion The iPROACTIVE trial represents the first interprofessional randomized controlled trial to evaluate a deprescribing service of hospital-initiated opioids. The trial will demonstrate whether an interprofessional counselling service can reduce opioid use in hospitalized adults without compromising safety or pain control. This study protocol provides a transferable model, adoptable to other hospitals to evaluate and implement their own opioid deprescribing strategies. Trial Registration The trial is registered with the German Clinical Trials Register (DRKS00036364) since 21 May 2025.