Clinical trial NCT05229055: Intranasal Ketamine Versus Subcutaneous Ketamine for Treatment of Post-traumatic Acute Pain in the Emergency Department ( INVESCK )
Official title: Intranasal Ketamine Versus Subcutaneous Ketamine for Treatment of Post Traumatic Acute Pain in the Emergency Department
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute Pain
Lead sponsor: University of Monastir
Sponsor class: OTHER
First posted: 2022-02-08
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The intranasal route Ketamine solution was used. Applying a nasal spray pump where each spray delivered 20 mg of ketamine. After initial evaluation, each patient having the inclusion criteria receives one pulverisation (0.4 ml) per nostril of ketamine corresponding to a total dose of 20 mg of ketamine.

The subcutaneous route :

Ketamine dosing by subcutanous route was based on previous reports use for post operative pain management. . The results of these reports revealed that low-dose ketamine 20-60 mg (0.5mg/kg for patients weighing 40-120 kg) showed an over all decrease in either the amount of opioid used or the amount of pain experienced (10, 11). For our study, we decided to chose a dose of 20mg of ketamine for all patients administered via 1ml insulin syringe once subcutaneously.
Primary purpose: TREATMENT

Brief summary: Pain is the most common complaint for emergency department (ED) visit. Intranasal ketamine has been shown to provide rapid, well-tolerated, effective analgesia to emergency department (ED) patients with acute pain. few trials have studied ketamine infusion subcutaneously for pain management in trauma patients.

Detailed description: Materials and methods :

Study design It is a randomized, prospective, double blind, controlled, multicentric trial.

Study setting and selection of participants :

The trial is conducted in three community teaching hospitals :

* Emergency department, fattouma bourgiba university hospital, monastir, tunisia.
* Emergency department, sahloul university hospital, sousse, tunisia.
* Emergency department, farhat hached university hospital, sousse, tunisia.

Inculsion criteria :

The study includes patients aged 18 to 60 years who presented to the ED with acute limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11 point (0-10). An informed consent is necessary. Pain was considered traumatic if it is reported as appearing immediately after the trauma and no anterior pain was described in the same limb.

The intranasal route Ketamine solution 250 mg/5ml was used. It was applied intranasally using a nasal spray pump where each spray delivered approximately 0.4 ml of solution corresponding to 20 mg of ketamine. After initial evaluation, each patient having the inclusion criteria receives one pulverisation (0.4 ml) per nostril of ketamine corresponding to a total dose of 20 mg of ketamine. Ketamine dosing was based on previous reports of intranasal ketamine use in ED patients, doses ranged from 0.45mg/kg to 1.25mg/kg.

The subcutaneous route :

Ketamine dosing by subcutanous route was based on previous reports use for post operative pain management. . The results of these reports revealed that low-dose ketamine 20-60 mg (0.5mg/kg for patients weighing 40-120 kg) showed an over all decrease in either the amount of opioid used or the amount of pain experienced. the investigators decided to chose a dose of 20mg of ketamine for all patients administered via 1ml insulin syringe once subcutaneously.

Protocol :

After initial medical evaluation, every patient who meet the inclusion criteria, will receive randomly either subcutaneous or intanasal dose of ketamine as detailed above according to the predetermined randomization. To ensure a double-blind administration of ketamine ; patients enrolled in the intranasal ketamine group will receive concomitantly 1ml of normal saline solution subcutaneously, and patients enrolled in the subcutaneous ketamine group will receive concomitantly a spray of normal saline solution in each nostril. None of the treating physician or nurses are aware about the medication received. The included patients were followed and monitored until their discharge from the ED. All enrolled patients underwent close supervision of study staff to ensure safety. Study investigators record VAS, and adverse effects at 15, 30, 60, 90, and 120 minutes and at ED discharge. During ED stay, patients were monitored in order to evaluate the need for rescue analgesic treatment. At 30 minutes, if patients report a pain numeric rating scale score of 5 or greater and request additional pain relief, titrated morphine is adminstered as a rescue analgesic with a dose of 0.1mg/kg repeated every 3 to 5 minutes if the pain numeric rating scale score is still greater or equal to 3.

. Patients's informed consent is obtained.

Eligibility criteria: Inclusion Criteria:

* • Patients who presented to the ED with acute limb trauma pain with a visual analgesic scale (VAS) of 5 or more on a standard 11 point (0-10).

  * Pain was considered traumatic if it is reported as appearing immediately after the trauma and no anterior pain was described in the same limb.

Exclusion Criteria:

* Pregnancy/Breastfeeding

  * altered mental status (GCS\<15)
  * Allergy to ketamine or morphine
  * Weight less than 40 kg or greater than 100kg
  * Unstable vital signs (systolic blood pressure \<90 or \> 180mmHg, pulse rate\<50 or \>150bpm, and respiration rate \<10 or \>30 breath/min)
  * Medical history of acute head or eye injury
  * Medical history of seizure
  * Medical history of intracranial hypertension,
  * Medical history of chronic pain,
  * Medical history of severe renal or hepatic insufficiency.
  * Medical history of glaucoma
  * Alcohol or drug abuse
  * Psychiatric illness,
  * Recent (4 hours before) analgesic agent use.

Primary outcomes:
measure: VAS decrease of more than 50% comparing to initial value at 30 minutes following analgesia administration
timeFrame: 30 minutes
measure: rate of severe adverse events
timeFrame: 120 minutes
Secondary outcomes:
measure: rate of rescue analgesia 1 doses of morphine required to reach efficient analgesia
timeFrame: 30 minutes
measure: rate of rescue analgesia 2 doses of morphine required to reach efficient analgesia
timeFrame: 120 minutes
Other outcomes:
Locations:
city: Monastir
country: Tunisia
facility: university of Monastir
Study officials:
affiliation: University of Monastir
name: Nouira Semir, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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