Fentanyl or esketamine for traumatic pain (FORE-PAIN) trial: study protocol for a double-blind multi-arm randomized non-inferiority trial.
Midas N de Grunt, Nurseda Risvanoglu, Johannes A Siegers, Maurice A G M Kroon, Maruschka P Merkus, Markus W Hollmann, Milan L Ridderikhof, Robert P Weenink
Trials May 26, 2025 DOI: 10.1186/s13063-025-08869-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Population | Adult subjects receiving emergency care from Emergency Medical Services Ambulance Amsterdam and suffering from acute severe traumatic pain |
| Interventions | Fentanyl Esketamine |
| Dose | fentanyl IV 1.0 µg/kg, fentanyl IN 1.25 µg/kg, esketamine IV 0.2 mg/kg, esketamine IN 0.625 mg/kg |
| Topics | Esketamine |
| Keywords | Emergency medicine Pain management Trauma care Acute pain Analgesia Emergency medical services Fentanyl Intranasal Intravenous Wounds and injuries Analgesic drugs Drug administration routes |
| Citations | 1 |
| Registration | NCT06051227 |
| Key findings | The trial aims to assess whether fentanyl IN, esketamine IV, and esketamine IN are non-inferior to fentanyl IV for reducing acute traumatic pain in the prehospital setting. |
Abstract
Although fentanyl and esketamine, administered intravenously (IV) or intranasally (IN), are standard of care for treatment of acute traumatic pain in the prehospital setting in the Netherlands, comparative evidence regarding their efficacy and safety is lacking. Therefore, this study aims to assess the efficacy and safety of fentanyl IN, esketamine IV and esketamine IN as compared to fentanyl IV for management of acute traumatic pain in the prehospital setting. This is a double-blind, monocenter, multi-arm, randomized non-inferiority trial in the prehospital setting in the Netherlands. Adult subjects receiving emergency care from Emergency Medical Services Ambulance Amsterdam and suffering from acute severe traumatic pain are randomized in an 1:1:1:1 ratio to receive fentanyl IV (1.0 µg/kg), fentanyl IN (1.25 µg/kg), esketamine IV (0.2 mg/kg), or esketamine IN (0.625 mg/kg). The primary endpoint is the reduction in Numeric Rating Scale (NRS, 0-10) score at 10 min after first administration of study medication. The prespecified non-inferiority margin is 1.0 for the between-group absolute difference in primary outcome. The primary endpoint is analyzed according to the intention-to-treat and per-protocol principles conforming to recommendations for non-inferiority analysis. Other endpoints include reduction in NRS score at other timepoints, need for additional analgesia, patient satisfaction, and adverse events. This trial is one of few double-blind randomized controlled trials in the prehospital setting and aims to answer questions that have relevance to prehospital practice. Research in a prehospital emergency setting also comes with challenges, including concerns about prehospital data quality, limited research experience among personnel and a limited timeframe for data collection and follow-up. Also, informed consent needs to be deferred. ClinicalTrials.gov NCT06051227. Registered on 9 September 2023.
Comparable studies
Other randomized controlled trials on esketamine, most cited first.
Citations in the library
Cites 2
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. Journal of Pharmacology and Experimental Therapeutics March 1, 1992