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

Limb Injury Clinical Trial

— ANTAMIN  

Official title:

Pain Reduction for Limb Injuries in Pediatric Emergency Departments: A Randomised Clinical Trial Comparing Intranasal Fentanyl or Intranasal Ketamine to Oral Morphine

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06464146
• Other study ID #: APHP211044
• Secondary ID: 2023-506803-25
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 2024
• Est. completion date: September 2027

Study information

• Verified date: June 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Hélène CHAPPUY, MD, PhD
• Phone: +33 1 44 49 41 26
• Email: helene.chappuy[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: September 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Emergencies
• Limb Injury
• Wounds and Injuries

Intervention

Drug:
• Morphine
oral morphine (0.5 mg / kg)
• IN fentanyl
IN fentanyl (1.5 µg/kg)
• IN ketamine
IN ketamine (1 mg/kg)
• NaCl 0,9 %
Injectable solution used as Placebo of Oral morphine or IN fentanyl/ ketamine.

Locations

Country	Name	City	State
France	Hopital Necker Enfants malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Reduction in pain (M15)	Reduction in pain from baseline assessed by Evendol for children <7 years	15 minutes
Secondary	Reduction in pain (M15)	Reduction in pain from baseline assessed by VAS for children = 7 years	15 minutes
Secondary	Reduction in pain (M30)	Reduction in pain from baseline assessed by Evendol for children <7 years	30 minutes
Secondary	Reduction in pain (M30)	Reduction in pain from baseline assessed by VAS for children = 7 years	30 minutes
Secondary	Reduction in pain (M60)	Reduction in pain from baseline assessed by Evendol for children <7 years	60 minutes
Secondary	Reduction in pain (M60)	Reduction in pain from baseline assessed by VAS for children = 7 years	60 minutes
Secondary	Reduction in pain (M90)	Reduction in pain from baseline (assessed by Evendol for children <7 years, by VAS for children = 7 years)	90 minutes
Secondary	Reduction in pain (M90)	Reduction in pain from baseline assessed by Evendol for children <7 years	90 minutes
Secondary	Reduction in pain (M120)	Reduction in pain from baseline by VAS for children = 7 years	120 minutes
Secondary	Degree of pain (M30) for comparison ketamine vs fentanyl	Success pain evaluation, as defined in primary outcome (for the comparison between ketamine and fentanyl)	30 minutes
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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