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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Pain Due to Trauma, Analgesia, Fentanyl, Esketamine, Emergency Medical Services

Intervention / Treatment
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* Drug: Fentanyl Citrate
* Drug: Esketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years pain has been caused by a trauma (any trauma mechanism) that occurred on the same day Emergency Medical Services personnel 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fentanyl IV<br>Opioid analgesic Form: fentanyl solution for injection/infusion Administration: intravenous Initial dose: 1 ug/kg Second dose (if required): 0.6ug/kg | Drug: Fentanyl Citrate<br>* Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal<br>|
| Experimental: Fentanyl IN<br>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 | Drug: Fentanyl Citrate<br>* Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal<br>|
| Experimental: Esketamine IV<br>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 | Drug: Esketamine<br>* Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal<br>|
| Experimental: Esketamine IN<br>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 | Drug: Esketamine<br>* Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain score as measured with Numeric Rating Scale (NRS) | NRS is an 11 point Likert scale ranging from 0 to 10, where 0 means 'no pain' and 10 means 'worst pain imaginable' | 10 minutes after first drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain score as measured with NRS | 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) | 
| Relative change in pain score as measured with NRS | 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) | 
| Number of subjects requiring a second dose of study medication | If the patient requires additional analgesia, study medication can be repeated once | 10 and 20 minutes after first drug administration | 
| Patient satisfaction with pre-hospital analgesia | Patient satisfaction is measured using an 11 point Likert scale ranging from 0 to 10, where 0 means 'extremely unsatisfactory' and 10 means 'extremely satisfactory' | Time of arrival at the hospital (expected within 30 minutes after first drug administration) | 
| Number of patients experiencing adverse events | Including side effects | Up to time of arrival at the hospital (expected within 30 minutes after first drug administration) | 
| Number of patients requiring unblinding | E.g. because of treatment failure or side effects | Up to time of arrival at the hospital (expected within 30 minutes after first drug administration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Analgesics, Ketanest, Administration, intranasal, Administration, intravenous, Pain management, Drug-Related Side Effects and Adverse Reactions, Anesthetics