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

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: Limb Injury

Treatments: Drug: NaCl 0,9 %; Drug: Morphine; Drug: IN fentanyl; Drug: IN ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT06464146

2023-506803-25 (EudraCT Number)

APHP211044

Details and patient eligibility

About

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.

Full 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.

Enrollment: 300 estimated patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

300 participants in 3 patient groups

Morphine

Active Comparator group

Description:

Oral morphine (0.5mg/kg) and IN placebo

Treatment:

Drug: Morphine

Drug: NaCl 0,9 %

IN Fentanyl

Experimental group

Description:

placebo of oral morphine and IN fentanyl (1.5 µg/kg)

Treatment:

Drug: IN fentanyl

Drug: NaCl 0,9 %

IN Ketamin

Experimental group

Description:

placebo of oral morphine and IN ketamine (1 mg/kg)

Treatment:

Drug: IN ketamine

Drug: NaCl 0,9 %