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

NCT06051227 | Recruiting Phase 3

• 4 other identifiers: FP-20232022-500176-63-00U1111-1287-74862022-000039-22
• Study Type: interventional
• Target: 608
• Locations: 1 country
• Sites: 1

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

Keywords

Analgesics; Ketanest; Administration, intranasal; Administration, intravenous; Pain management; Drug-Related Side Effects and Adverse Reactions; Anesthetics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in pain score as measured with NRS

  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

  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

  10 and 20 minutes after first drug administration

• Patient satisfaction with pre-hospital analgesia

  Time of arrival at the hospital (expected within 30 minutes after first drug administration)

• Number of patients experiencing adverse events

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

Study Arms (4)

Fentanyl IV

ACTIVE COMPARATOR

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

Fentanyl IN

EXPERIMENTAL

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

Esketamine IV

EXPERIMENTAL

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

Esketamine IN

EXPERIMENTAL

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

Interventions

Fentanyl Citrate DRUG

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

Fentanyl IN; Fentanyl IV

Esketamine DRUG

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

Esketamine IN; Esketamine IV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• (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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• Stichting ZiektekostenVerzekering Krijgsmacht: collaborator
• Ambulance Amsterdam: collaborator

Study Sites (1)

Ambulance Amsterdam

Amsterdam, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 40420189 DERIVED

MeSH Terms

Conditions

Agnosia; Drug-Related Side Effects and Adverse Reactions

Interventions

Fentanyl; Esketamine

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Markus W Hollmann, Prof. dr. dr.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert P Weenink, PhD

CONTACT

+31 205669111; forepain@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 22, 2023
• Study Start: January 11, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: January 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Metadata are published before locking of the database. The final data are published at the time of the journal article's publication.
• Access Criteria: 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.

Locations

NL (1)