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
- Are there results?
- None posted in the registry
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
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fentanyl OR Esketamine for Traumatic PAIN (FORE-PAIN) Trial
- ClinicalTrials.gov ID
- NCT06051227
- Acronym / sponsor ID
- FORE-PAIN / FP-2023
- Keywords
- Analgesics, Ketanest, Administration, intranasal, Administration, intravenous, Pain management, Drug-Related Side Effects and Adverse Reactions, Anesthetics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow recruitment.
- Enrolment
- 235 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Stichting ZiektekostenVerzekering Krijgsmacht, Ambulance Amsterdam
- Study start
- 11 Jan 2024 (actual)
- Primary completion
- 6 Aug 2026 (actual)
- Study completion
- 6 Aug 2026 (actual)
- First posted
- 22 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Fentanyl IV | Active comparator | Drug: Fentanyl CitrateOpioid analgesic Form: fentanyl solution for injection/infusion Administration: intravenous Initial dose: 1 ug/kg Second dose (if required): 0.6ug/kg |
| Fentanyl IN | Experimental | Drug: Fentanyl CitrateOpioid 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 |
| Esketamine IV | Experimental | Drug: EsketamineAnesthetic, 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 |
| Esketamine IN | Experimental | Drug: EsketamineAnesthetic, 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- (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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fentanyl CitrateSubjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal | Drug | Fentanyl IN, Fentanyl IV |
| EsketamineSubjects receive one dose of study medication (fentanyl or esketamine) at baseline, either intravenous or intranasal | Drug | Esketamine IN, Esketamine IV |
Primary outcome
Change in pain score as measured with Numeric Rating Scale (NRS)
Time frame: 10 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'
6 secondary outcomes
Change in pain score as measured with NRS
Time frame: 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
Time frame: 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
Time frame: 10 and 20 minutes after first drug administration
Patient satisfaction with pre-hospital analgesia
Time frame: Time of arrival at the hospital (expected within 30 minutes after first drug administration)
Number of patients experiencing adverse events
Time frame: Up to time of arrival at the hospital (expected within 30 minutes after first drug administration)
Number of patients requiring unblinding
Time frame: Up to time of arrival at the hospital (expected within 30 minutes after first drug administration)
Results and safety
The study was stopped early (reason given: slow recruitment.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Derived from this study: PubMed 40420189de 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.
- Individual participant dataSharing planned: Yes. Metadata and final data will be published. Conditions for reuse apply.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Markus W Hollmann, Prof. dr. dr. principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow recruitment.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in pain score as measured with Numeric Rating Scale (NRS) (time frame: 10 minutes after first drug administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06051227, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.