Acute Pain Due to TraumaPhase 3FORE-PAINNCT06051227
Fentanyl OR Esketamine for Traumatic PAIN (FORE-PAIN) Trial
A Phase 3 study testing Fentanyl Citrate and Esketamine in people with Acute Pain Due to Trauma and Analgesia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Pain Due to Trauma, Analgesia, Fentanyl
- What is being tested?
- Fentanyl Citrate and Esketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 235 participants
- Where
- 1 siteNetherlands
- Study dates
- 11 Jan 2024to 6 Aug 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- (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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Being tested
- Fentanyl Citrate, Esketamine
- Keywords
- Analgesics, Ketanest, Administration, intranasal, Administration, intravenous, Pain management, Drug-Related Side Effects and Adverse Reactions, Anesthetics
- Medical subject headings
- Agnosia, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fentanyl CitrateDrug
Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal
EsketamineDrug
Subjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Esketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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'
Measured: 10 minutes after first drug administration
Secondary outcomes (6)
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'
Measured: 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'
Measured: 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
Measured: 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'
Measured: Time of arrival at the hospital (expected within 30 minutes after first drug administration)
Number of patients experiencing adverse events
Including side effects
Measured: 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
Measured: Up to time of arrival at the hospital (expected within 30 minutes after first drug administration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2023
- Study start11 Jan 2024
- Primary completion6 Aug 2026
- Study completion6 Aug 2026
Why it stopped: slow recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Pain Due to TraumaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 235 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Sponsor type
- University, hospital or other
- Collaborators
- Stichting ZiektekostenVerzekering Krijgsmacht, Ambulance Amsterdam
- Responsible party
- Principal investigator, Robert Weenink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Markus W Hollmann, Prof. dr. dr., Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06051227
- Sponsor's protocol ID
- FP-2023
- Other IDs
- 2022-500176-63-00, U1111-1287-7486, 2022-000039-22
- Acronym
- FORE-PAIN
- Status last verified
- Sep 2026
- First submitted
- 13 Sep 2023
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Metadata and final data will be published. Conditions for reuse apply.
Publications
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.
PubMed 40420189