Efficacy and safety of sivelestat sodium hydrate adjunct to remifentanil for analgesia in patients under mechanical ventilation (SIDING trial): protocol of a multicenter, randomized, double-blinded, placebo-controlled trial

IntroductionInadequate analgesia is associated with worse outcomes in patients under mechanical ventilation. Current guidelines recommend opioids as the first-line analgesics. However, prolonged use of opioids is associated with numerous adverse effects. Preclinical studies have shown that sivelestat sodium hydrate attenuates pain-related behaviours in rodent models; however, its analgesic and opioid-sparing effects in humans remain unknown. This study aims to investigate whether sivelestat reduces remifentanil requirements while maintaining adequate analgesia in mechanically ventilated patients.Methods and analysisThis multicenter, randomized, double-blinded, placebo-controlled trial is conducted in seven ICUs across China. 136 patients under mechanical ventilation will be randomly assigned to the placebo and sivelestat groups at a 1:1 ratio. The study drug will be administered at an initial rate of 0.2 mg/kg/h, as an adjunct to a standard remifentanil-based analgesic regimen. Remifentanil will be used as the protocolized background analgesic, with rescue analgesics permitted when predefined criteria are met. The primary outcome is mean hourly remifentanil consumption per kilogram during the intervention period.Ethics and disseminationThis study has been approved by the ethics committee of The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University (KY-2024-093-01) and all participating sites. Results will be disseminated through peer-reviewed journals and scientific conferences.Study Protocol Registrationhttps://www.chictr.org.cn, identifier ChiCTR2400086632.