Limb InjuryPhase 3ANTAMINNCT06464146
Pain Reduction for Limb Injuries in Pediatric Emergency Departments: Intranasal Fentanyl or Intranasal Ketamine vs Oral Morphine
A Phase 3 study testing Morphine, IN fentanyl and IN ketamine in people with Limb Injury, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.
Trial summary
The purpose of this study is to determine if IN fentanyl (1.5 µg/kg) or IN ketamine (1 mg/kg) is more effective at 30 minutes than oral morphine (0.5 mg/kg) in reduction of moderate and severe pain associated with limb injuries in patients 2-17 years of age presenting to the ED. Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Limb Injury
- What is being tested?
- Morphine, IN fentanyl and IN ketamine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 5 sitesFrance
- Study dates
- 26 Feb 2025to Feb 2028
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Child aged 2 years to 17 years and 11 months
- With 10 kg ≤ Weight ≤ 100 kg
- Presenting to ED with a traumatic pain and suspected fracture(s) based on an acute deformity AND experiencing pain and/or functional impotence in the injured limb(s)
- Within the first 12 hours after the injury
- VAS pain score at ED arrival ≥ 60/100 (if child ≥ 7 years) or Evendol pain score at ED arrival ≥ 7/15 (if child < 7 years)
- Affiliated to health insurance
- At least one signed parental informed consent
Who cannot join
- Received narcotic pain medication prior to arrival
- Contraindication to morphine, mentioned in SmPC
- Hypersensitivity to ketamine or fentanyl or to excipients (sodium chloride, sodium hydroxide), or to other opioids.
- Contraindication to fentanyl or ketamine, mentioned in SmPC
- GCS <15
- Evidence of significant femur, head, chest, abdominal, or spine injury
Show all 16Show fewer
- Open fracture
- Nasal trauma or complete nasal obstruction
- Active epistaxis
- Nasal or sinus surgery within 6 months before inclusion
- History of high blood pressure, known coronary artery disease, congestive heart failure, acute glaucoma, increased intracranial pressure, major psychiatric disorder, hepatocellular insufficiency
- Active or history of psychiatric disorder
- Known pregnancy or suspicion of being pregnant
- Breastfeeding
- Non-French speaking parent and / or child.
- Participation to another interventional clinical research
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
Ambroise Paré Hospital
Boulogne-Billancourt, 92100
Marlène MICHELON JOUNEAUX, MD, PhD, 01 49 09 57 00, marlene.michelonjouneaux@aphp.fr
Marlène MICHELON JOUNEAUX
- Recruiting
Roger Salengro Hospital
Lille, 59000
Melany LIBER, MD, PhD, 03 20 44 46 64 ext. +33, melany.liber@chu-lille.fr
Melany LIBER
- Recruiting
Timone Hospital
Marseille, 13005
Aurélie MORAND, MD, PHD, 04 91 38 96 99 ext. +33, aurelie.morand@ap-hm.fr
Aurélie MORAND
- Recruiting
Mère-Enfant Hospital
Nantes, 44000
Adeline BOUCHERON, 02 44 76 84 79 ext. +33, adeline.boucheron@chu-lille.fr
Adeline BOUCHERON
- Recruiting
Hopital Necker Enfants malades
Paris, 75015
Hélène CHAPPUY, MD, PhD, +33 1 44 49 41 26 ext. +33, helene.chappuy@aphp.fr
About this study
Official title: Pain Reduction for Limb Injuries in Pediatric Emergency Departments: A Randomised Clinical Trial Comparing Intranasal Fentanyl or Intranasal Ketamine to Oral Morphine
The purpose of this study is to determine if IN fentanyl (1.5 µg/kg) or IN ketamine (1 mg/kg) is more effective at 30 minutes than oral morphine (0.5 mg/kg) in reduction of moderate and severe pain associated with limb injuries in patients 2-17 years of age presenting to the ED.
Read the detailed description
In children with moderate to severe pain due to musculoskeletal injuries, the first-line analgesic therapy in pediatric emergency departments (ED) is oral or intravenous morphine. Due to the delay or discomfort associated with establishing IV access, oral forms are preferred in French ED. Unfortunately, oral morphine alone or with ibuprofen or paracetamol, none regimen is optimal for relieving pain in children with traumatic limb injuries. However, the use of intranasal course is a safe route that can provide rapid and almost immediate analgesia. Intranasal administration is easy, non-invasive and usually well tolerated by children. In the last years, drugs with analgesic and sedative properties is increasing, particularly on fentanyl, ketamine, which can be also administered by the IN route. There are currently no studies, neither published nor ongoing, which compare IN fentanyl or IN ketamine to a standard oral morphine for children with acute moderate to severe pain with limb injuries presenting to the ED. The main hypothesis is that the efficacy of the analgesia 30 minutes after the administration will be higher with IN Fentanyl or with IN Ketamine, when compared to oral morphine.
- Conditions
- Limb Injury
- Being tested
- Morphine, IN fentanyl, IN ketamine, NaCl 0,9 %
- Keywords
- Fentanyl, Ketamin, Limb injury, Pain, Children
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
oral morphine (0.5 mg / kg)
IN fentanylDrug
IN fentanyl (1.5 µg/kg)
IN ketamineDrug
IN ketamine (1 mg/kg)
NaCl 0,9 %Drug
Injectable solution used as Placebo of Oral morphine or IN fentanyl/ ketamine.
| Study group | Role | What they receive |
|---|---|---|
| Morphine | Active comparator | Oral morphine (0.5mg/kg) and IN placebo Receives: Drug: Morphine; Drug: NaCl 0,9 % |
| IN Fentanyl | Experimental | placebo of oral morphine and IN fentanyl (1.5 µg/kg) Receives: Drug: IN fentanyl; Drug: NaCl 0,9 % |
| IN Ketamin | Experimental | placebo of oral morphine and IN ketamine (1 mg/kg) Receives: Drug: IN ketamine; Drug: NaCl 0,9 % |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of pain (M30)
Success: children <7 years with a pain score assessed by Evendol < 5 years, 30 minutes after drugs administration, without rescue analgesia. Scale: 0-15 (no pain - painful)
Measured: 30 minutes
Degree of pain (M30)
Success: children ≥ 7 years with pain score assessed by VAS ≤ 30, 30 minutes after drugs administration, without rescue analgesia. Visual Analog Scale : 0-100 (no pain- painful)
Measured: 30 minutes
Secondary outcomes (29)
Degree of pain (M15)
Success: children <7 years with a pain score assessed by Evendol < 5, 15 minutes after drugs administration, without rescue analgesia
Measured: 15 minutes
Degree of pain (M15)
Success: children ≥ 7 years with pain score assessed by VAS ≤ 30, 15 minutes after drugs administration, without rescue analgesia
Measured: 15 minutes
Degree of pain (M60)
Success: children <7 years with a pain score assessed by Evendol < 5, 60 minutes after drugs administration, without rescue analgesia
Measured: 60 minutes
Degree of pain (M60)
Success: children ≥ 7 years with pain score assessed by VAS ≤ 30, 60 minutes after drugs administration, without rescue analgesia
Measured: 60 minutes
Degree of pain (M90)
Success: children <7 years with a pain score assessed by Evendol < 5, 90 minutes after drugs administration, without rescue analgesia
Measured: 90 minutes
Degree of pain (M90)
Success: children ≥ 7 years with pain score assessed by VAS ≤ 30, 90 minutes after drugs administration, without rescue analgesia
Measured: 90 minutes
Degree of pain (M120)
Success: children <7 years with a pain score assessed by Evendol < 5, 120 minutes after drugs administration, without rescue analgesia
Measured: 120 minutes
Degree of pain (M120)
Success: children ≥ 7 years with pain score assessed by VAS ≤ 30, 120 minutes after drugs administration, without rescue analgesia
Measured: 120 minutes
Reduction in pain (M15)
Reduction in pain from baseline assessed by Evendol for children <7 years
Measured: 15 minutes
Reduction in pain (M15)
Reduction in pain from baseline assessed by VAS for children ≥ 7 years
Measured: 15 minutes
Reduction in pain (M30)
Reduction in pain from baseline assessed by Evendol for children <7 years
Measured: 30 minutes
Reduction in pain (M30)
Reduction in pain from baseline assessed by VAS for children ≥ 7 years
Measured: 30 minutes
Reduction in pain (M60)
Reduction in pain from baseline assessed by Evendol for children <7 years
Measured: 60 minutes
Reduction in pain (M60)
Reduction in pain from baseline assessed by VAS for children ≥ 7 years
Measured: 60 minutes
Reduction in pain (M90)
Reduction in pain from baseline (assessed by VAS for children ≥ 7 years)
Measured: 90 minutes
Reduction in pain (M90)
Reduction in pain from baseline assessed by Evendol for children <7 years
Measured: 90 minutes
Reduction in pain (M120)
Reduction in pain from baseline assessed by VAS for children ≥ 7 years
Measured: 120 minutes
Reduction in pain (M120)
Reduction in pain from baseline assessed by EVENDOL for children < 7 years
Measured: 120 minutes
Degree of pain (M30) for comparison ketamine vs fentanyl
Success pain evaluation, as defined in primary outcome (for the comparison between ketamine and fentanyl) assessed by Evendol for children <7 years
Measured: 30 minutes
Degree of pain (M30) for comparison ketamine vs fentanyl
Success pain evaluation, as defined in primary outcome (for the comparison between ketamine and fentanyl) assessed by VAS for children ≥ 7 years
Measured: 30 minutes
Level of sedation (M5)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 5 minutes
Level of sedation (M10)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 10 minutes
Level of sedation (M15)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 15 minutes
Level of sedation (M30)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 30 minutes
Level of sedation (M60)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 60 minutes
Level of sedation (M90)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 90 minutes
Level of sedation (M120)
Level of sedation as measured by the University of Michigan Sedation Scale Score (UMSS) after drugs administration, from 0 (patient awake) to 4 (patient unawakable)
Measured: 120 minutes
Number of participants with Adverse events
Adverse events potentially associated with IN ketamine, IN fentanyl and/or oral morphine: drowsiness, dizziness, pruritus, nausea, vomiting, dysphoria, nasal burning and irritation, unpleasant taste, vision changes, throat irritation, headache, vital sign changes (heart rate, respiratory rate, oxygen saturation, blood pressure).
Measured: From study treatment intake until ED discharge, up to 1 day
Score of satisfaction
General satisfaction of parents and patient ≥ 7 years old on a scale of 0-100 with corresponding faces (0 = no satisfaction at all, 100 = very satisfied)
Measured: At ED discharge, up to 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2024
- Study start26 Feb 2025
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Limb InjuryStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Hélène CHAPPUY, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06464146
- Sponsor's protocol ID
- APHP211044
- Other IDs
- 2023-506803-25, 2023
- Acronym
- ANTAMIN
- Status last verified
- Mar 2026
- First submitted
- 3 Jun 2024
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No