Fentanyl OR Esketamine for Traumatic PAIN (FORE-PAIN) Trial (FORE-PAIN)

Fentanyl and esketamine are both standard of care for treatment of acute severe traumatic pain in the prehospital setting in the Netherlands. However, it is not known whether they are equally effective and safe. It is also not known whether intranasal (IN) administration of fentanyl or esketamine is equally effective and safe as intravenous (IV) administration. The FORE-PAIN trial is a double-blind multi-arm randomized non-inferiority trial comparing Fentanyl IN, esketamine IV and esketamine IN (intervention arms) to fentanyl IV (comparator arm) for prehospital management of traumatic pain. The investigators hypothesize that all intervention arms provide analgesia that is non-inferior to the comparator arm, and that all study arms are equally safe.

Analgesics, opioid, Analgesics, non-narcotic, Analgesics, narcotic, Analgesics, Fentanyl, Esketamine, Administration, intranasal, Administration, intravenous, Pain management, Drug-Related Side Effects and Adverse Reactions, Anesthetics, Anesthetics, dissociative

Opioid analgesic Form: fentanyl solution for injection/infusion Administration: intravenous Initial dose: 1 ug/kg Second dose (if required): 0.6ug/kg

Opioid analgesic Form: fentanyl solution for injection/infusion Administration: intranasal using nasal atomizer Initial dose: 1.25 ug/kg to a maximum of 100ug Second dose (if required): 1ug/kg to a maximum total dose of 2ug/kg

Anesthetic, in lower doses the analgesic effect is dominant Form: esketamine solution for injection/infusion Administration: intravenous Initial dose: 0.2mg/kg Second dose (if required): 0.12mg/kg

Anesthetic, in lower doses the analgesic effect is dominant Form: esketamine solution for injection/infusion Administration: intranasal using a nasal atomizer Initial dose: 0.625mg/kg to a maximum of 50mg Second dose (if required): 0.5mg/kg to a maximum total dose of 1mg/kg

Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal

Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal

NRS is an 11 point Likert scale ranging from 0 to 10, where 0 means 'no pain' and 10 means 'worst pain imaginable'

NRS is an 11 point Likert scale ranging from 0 to 10, where 0 means 'no pain' and 10 means 'worst pain imaginable'

20 minutes after first drug administration; time of arrival at the hospital (expected within 30 minutes after first drug administration)

NRS is an 11 point Likert scale ranging from 0 to 10, where 0 means 'no pain' and 10 means 'worst pain imaginable'

10 and 20 minutes after first drug administration; time of arrival at the hospital (expected within 30 minutes after first drug administration)

NRS score is used to measure satisfaction. NRS is an 11 point Likert scale ranging from 0 to 10, where 0 means 'extremely unsatisfactory' and 10 means 'extremely satisfactory'

Inclusion Criteria: age ≥ 18 years pain has been caused by a trauma (any trauma mechanism) that occurred on the same day PP determines that administration of a strong opioid or esketamine for analgesia is required patient will be transported to a hospital Exclusion Criteria: (estimated) weight <40 or >100 kg subject does not understand Dutch or English inability to report pain score inability to give IN or IV medication known severe cardiovascular disease pre-eclampsia Glasgow Coma Scale score < 11 subject is known to have previously declined participation in medical research

Metadata are published before locking of the database. The final data are published at the time of the journal article's publication.

Conditions for reuse of data are described in the patient information folder. Access to the data can be granted by the Principal Investigator based on these criteria.