Comparison of Oliceridine to Remifentanil for Optimal Analgesia in Mechanical Ventilation (CO-ROAM): Study Protocol for a Multicenter Randomized Controlled Trial.

Introduction: Critically ill patients often endure pain, a distressing experience that can trigger diverse pathophysiological consequences. While remifentanil, with its rapid kinetics, is commonly used for analgesia in intensive care units (ICU), it frequently leads to opioid-related adverse effects. A promising alternative has emerged in oliceridine, a novel G protein-biased μ-opioid receptor agonist. This new drug offers the potential for effective pain relief with fewer side effects. However, its efficacy and safety profile in mechanically ventilated ICU patients remain to be fully elucidated.

Methods: This is a multicenter, prospective, randomized, single-blind, active-controlled trial conducted across 24 ICUs in China. A total of 292 mechanically ventilated patients requiring analgesia and sedation will be randomly assigned in a 1:1 ratio to either the oliceridine or remifentanil group. The oliceridine group will receive oliceridine (2-20 μg/kg/h), while the remifentanil group will receive remifentanil (1.5-12 μg/kg/h). Both groups will receive propofol for sedation if necessary. The target for analgesia is Critical-Care Pain Observation Tool (CPOT) < 3, and for sedation is Richmond Agitation-Sedation Scale (RASS) - 2 to 0.

Planned Outcomes: The primary outcome will be the percentage of time within target analgesia during study drug administration. Secondary outcomes will include gastrointestinal dysfunction, respiratory depression, sedative usage, mechanical ventilation duration, ICU stay length, extubation failure rate, etc. TRIAL REGISTRATION: NCT06454292. Registered on June 11, 2024.