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

NCT ID: NCT06051227

Last Updated: 2025-01-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 608 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-11
• Study Completion Date: 2026-03-31

Brief Summary

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.

Conditions

Acute Pain Due to Trauma; Analgesia; Fentanyl; Esketamine; Emergency Medical Services

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Fentanyl IV

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

Group Type: ACTIVE_COMPARATOR

Fentanyl Citrate

Intervention Type: DRUG

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

Fentanyl IN

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

Group Type: EXPERIMENTAL

Fentanyl Citrate

Intervention Type: DRUG

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

Esketamine IV

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

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: DRUG

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

Esketamine IN

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

Group Type: EXPERIMENTAL

Esketamine

Intervention Type: DRUG

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

Interventions

Fentanyl Citrate

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

Intervention Type: DRUG

Esketamine

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stichting ZiektekostenVerzekering Krijgsmacht

UNKNOWN

Sponsor Role: collaborator

Ambulance Amsterdam

UNKNOWN

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Robert Weenink

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Markus W Hollmann, Prof. dr. dr.

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

Ambulance Amsterdam

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Robert P Weenink, PhD

Role: CONTACT

forepain@amsterdamumc.nl

+31 205669111

Facility Contacts

Midas de Grunt, MD

Role: primary

forepain@amsterdamumc.nl

References

de Grunt MN, Risvanoglu N, Siegers JA, Kroon MAGM, Merkus MP, Hollmann MW, Ridderikhof ML, Weenink RP. Fentanyl or esketamine for traumatic pain (FORE-PAIN) trial: study protocol for a double-blind multi-arm randomized non-inferiority trial. Trials. 2025 May 26;26(1):172. doi: 10.1186/s13063-025-08869-9.

Reference Type: DERIVED

PMID: 40420189 (View on PubMed)

Other Identifiers

2022-500176-63-00

Identifier Type: OTHER

Identifier Source: secondary_id

U1111-1287-7486

Identifier Type: OTHER

Identifier Source: secondary_id

2022-000039-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FP-2023

Identifier Type: -

Identifier Source: org_study_id