Pain Reduction for Limb Injuries in Pediatric Emergency Departments: Intranasal Fentanyl or Intranasal Ketamine vs Oral Morphine (ANTAMIN)

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.

Study Overview

• Status: Recruiting
• Conditions: Limb Injury
• Intervention / Treatment: Drug: Morphine; Drug: NaCl 0,9 %; Drug: IN fentanyl; Drug: IN ketamine

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hélène CHAPPUY, MD, PhD; Phone Number: +33 1 44 49 41 26; Email: helene.chappuy@aphp.fr
• Study Contact Backup: Name: Nelly BRIAND, PhD; Phone Number: 0144381862; Email: nelly.briand@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Recruiting
    • Ambroise Paré Hospital
    • Contact: Marlène MICHELON JOUNEAUX, MD, PhD; Phone Number: 01 49 09 57 00; Email: marlene.michelonjouneaux@aphp.fr
    • Principal Investigator: Marlène MICHELON JOUNEAUX
  • Lille, France, 59000
    • Recruiting
    • Roger Salengro Hospital
    • Contact: Melany LIBER, MD, PhD; Phone Number: +33 03 20 44 46 64; Email: melany.liber@chu-lille.fr
    • Principal Investigator: Melany LIBER
  • Marseille, France, 13005
    • Recruiting
    • Timone Hospital
    • Contact: Aurélie MORAND, MD, PHD; Phone Number: +33 04 91 38 96 99; Email: aurelie.morand@ap-hm.fr
    • Principal Investigator: Aurélie MORAND
  • Nantes, France, 44000
    • Recruiting
    • Mère-Enfant Hospital
    • Contact: Adeline BOUCHERON; Phone Number: +33 02 44 76 84 79; Email: adeline.boucheron@chu-lille.fr
    • Principal Investigator: Adeline BOUCHERON
  • Paris, France, 75015
    • Recruiting
    • Hopital Necker Enfants Malades
    • Contact: Hélène CHAPPUY, MD, PhD; Phone Number: +33 +33 1 44 49 41 26; Email: helene.chappuy@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine; Oral morphine (0.5mg/kg) and IN placebo	Drug: Morphine; oral morphine (0.5 mg / kg); Drug: NaCl 0,9 %; Injectable solution used as Placebo of Oral morphine or IN fentanyl/ ketamine.
Experimental: IN Fentanyl; placebo of oral morphine and IN fentanyl (1.5 µg/kg)	Drug: NaCl 0,9 %; Injectable solution used as Placebo of Oral morphine or IN fentanyl/ ketamine.; Drug: IN fentanyl; IN fentanyl (1.5 µg/kg)
Experimental: IN Ketamin; placebo of oral morphine and IN ketamine (1 mg/kg)	Drug: NaCl 0,9 %; Injectable solution used as Placebo of Oral morphine or IN fentanyl/ ketamine.; Drug: IN ketamine; IN ketamine (1 mg/kg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of pain (M15)	Success: children <7 years with a pain score assessed by Evendol < 5, 15 minutes after drugs administration, without rescue analgesia	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	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	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	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	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	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	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	120 minutes
Reduction in pain (M15)	Reduction in pain from baseline assessed by Evendol for children <7 years	15 minutes
Reduction in pain (M15)	Reduction in pain from baseline assessed by VAS for children ≥ 7 years	15 minutes
Reduction in pain (M30)	Reduction in pain from baseline assessed by Evendol for children <7 years	30 minutes
Reduction in pain (M30)	Reduction in pain from baseline assessed by VAS for children ≥ 7 years	30 minutes
Reduction in pain (M60)	Reduction in pain from baseline assessed by Evendol for children <7 years	60 minutes
Reduction in pain (M60)	Reduction in pain from baseline assessed by VAS for children ≥ 7 years	60 minutes
Reduction in pain (M90)	Reduction in pain from baseline assessed by Evendol for children <7 years	90 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	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	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)	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)	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)	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)	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)	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)	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)	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).	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)	At ED discharge, up to 1 day
Reduction in pain (M90)	Reduction in pain from baseline (assessed by VAS for children ≥ 7 years)	90 minutes
Reduction in pain (M120)	Reduction in pain from baseline assessed by VAS for children ≥ 7 years	120 minutes
Reduction in pain (M120)	Reduction in pain from baseline assessed by EVENDOL for children < 7 years	120 minutes

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Hélène CHAPPUY, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 12, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pain; Children; Fentanyl; Ketamin; Limb injury
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Morphine; Ketamine; Fentanyl
• Other Study ID Numbers: APHP211044; 2023-506803-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No